The speaker notices a flea and points it out to the woman he loves. The flea has bitten them both, and now their blood is mixed inside the flea. He says that no one would consider it a sin or shameful for their bodily fluids to mix inside a bug, so why don't they just swap fluids in bed?
Um, something to think about, we guess.
Now she (quite rationally) tries to kill the flea, but the speaker stops her. He says the flea represents the joining of their blood, as in marriage. If she squashes the flea, she will be killing herself, the speaker, and, oh-by-the-way, committing sacrilege against the institution of marriage.
Let's not get carried away here, Donne.
Splat. She kills the poor, innocent flea. She thinks this disproves the earlier claim that killing the flea would kill them both. But Donne, as always, has a comeback ready: the fact that she hasn't suffered from the death of the flea in which their bloods were mixed means that "swapping fluids" isn't so dangerous to her honor as she thinks. In straightforward terms, his point is: "You have nothing to fear from having sex with me."
What a charmer.