Of course, sometimes it does need to be followed by a comma, which can make things confusing.
Now that we've cleared that up ...
Those of you who subscribe to the “stick a comma wherever you hear a pause” school of punctuation may think the blog post should end here; after all, if you go back and read the two previous sentences aloud, the lack of pause after the first “of course” and the obvious pause after the second make the correct punctuation clear.
Well, when I first had the idea to write about this question, I didn’t think it warranted a whole blog post either. I’d been reading a lot of independently published novels on Kindle Unlimited, and in several different books I stumbled over dialogue like this:
"Did he agree to cat-sit for Mr. Whiskers?" "Of course, he didn't."
I was riding a metaphorical horse, cantering along in a smooth rhythm --- da da DA, da da DA, da da --- and the horse tripped. I was anticipating the next beat, but instead I was momentarily unsupported, suspended over a void. All because of a comma.
Despite being a copyeditor, I can overlook a fair amount of mistakes when I’m reading for pleasure. In fact, my ability to shut out distractions and immerse myself in a story is so powerful, I had to stick to non-fiction when my kids were small. (The sacrifice was worth it; they’re still alive and I'm pretty sure they don’t hate me.)
But those commas really bugged me.
Even though I was sure those commas were wrong, as a copyeditor I needed to understand why. But when I googled the title question, I found very little written about "of course" and commas, and in the few conversations I came across, people either expressed confusion or recalled being taught that "of course" did in fact always require commas. That was when I realized the topic needed its own blog post.
Perhaps those self-published authors --- aware that ears aren't enough when it comes to comma placement --- googled this same question and were thrown off. Because in this case, the ears have it.
Let's get down to the nitty gritty.
“Of course” is an adverbial phrase.
It belongs to a group of adverbs that can also act as conjunctions. Because of this split personality, these particular adverbs often lead to punctuation perplexity.
When these adverbs connect two independent clauses, they’re called conjunctive adverbs.
When they’re made up of two or more words (like “of course”), they’re called compound conjunctive adverbs or conjunctive adverbial phrases.
Unlike coordinating conjunctions like “and” or “but,” conjunctive adverbs don’t have the power to join independent clauses with a comma --- so they’re preceded by a semicolon and followed by a comma.
Cats can be a loving pets; however, they can’t compare to dogs.
These multipurpose adverbs can also show a relationship between two sentences. They introduce the second of the pair, and since they’re modifying the entire sentence and not just the verb, they’re acting as sentence adverbs and should be followed by a comma.
But dogs will love anyone. Also, they drool.
Conjunctive adverbs can also interrupt a clause. Unlike regular adverbs, which are only rarely set off by commas to add emphasis, conjunctive adverbs are usually set off by commas.
Cats, on the other hand, are particular and fastidious.
Sometimes, if a writer wants to de-emphasize the interruption, the commas can be left out.
You indeed believe that cats are a superior pet. I will therefore not engage you on this topic henceforth.
A few conjunctive adverbs (“however” being one of them) always require a stronger interruption and therefore need to be set off with commas. But if “however” is used to mean “in whatever manner” or “to whatever degree,” it is a simple adverb that's modifying the verb, not the entire clause, and isn't set off by commas.
However you argue your case, I will never prefer dogs over cats!
Which brings us back to "of course."
As a simple adverb
When “of course” is a simple adverb of agreement or emphasis—meaning “certainly,” “naturally,” “definitely,” and the like—it usually doesn’t require commas.
Of course you can go to the party!
But sometimes it does need a comma. (In the second sentence, a period could replace the comma.)
"May I read it? "Of course, I’d be honored!"
Notice how the meaning (and inflection) is changed when the comma is removed.
"Would you really be honored if that shady organization gave you an award?" "Of course I’d be honored!"
There are other exceptions as well. Simple adverbs can sometimes be set off by commas for emphasis. Compare the following sentences. They mean essentially the same thing and are both correct.
He will of course be subject to the same rules as everyone else.
He will, of course, be subject to the same rules as everyone else.
As a conjunctive adverb
When "of course" is used as a conjunctive adverb (meaning “on the other hand,” “as might be expected,” “nevertheless,” “still”) that introduces an independent clause, it will be punctuated as described above and shown in the example below.
I can’t stand that man; of course, he probably doesn’t care much for me either.
When the conjunctive adverb "of course" interrupts a clause, whether or not to use commas depends on the degree of interruption desired by the writer.
As a sentence adverb
When "of course" is used as a sentence adverb, it's followed by a comma.
I can't stand that man. Of course, he probably doesn't care much for me either.
So listen up.
When I began the grammar course for my copyediting certificate, I was confident in my punctuation ability. I knew the basic rules and could usually tell by the quality and length of a pause whether a comma was needed. But I quickly realized that, while my ear was good, it could only get me so far. Commas can be tricky, and there's no substitute for learning the rules.
Understanding the grammar underlying the rules is enormously helpful, especially when the rules depend on the context. If you’re able to recognize an introductory “of course” as a conjunctive adverb or a sentence adverb, you’ll know a comma needs to follow. But when “of course” is a simple adverb --- or a conjunctive adverb interrupting the clause --- there are no clear rules to guide you, and it’s important to read aloud and use your ears.
A comma represents a certain intonation, so careful listeners can usually hear where they belong. If a pause sounds wrong, it probably is. And if you’re still not sure? Ask a copyeditor.