Stanza 1 Summary

Get out the microscope, because we’re going through this poem line-by-line.

Mark but this flea, and mark in this,
How little that which thou deniest me is;

With a wave of his imaginary hand, the speaker gestures to a small flea that is sucking on the tender flesh of the woman he desires.
We don't know if he loves her or not just yet, and we may not find out. But she has denied him something. We're guessing this something is either physical, emotional, or both.
"Mark" in this context means, "Look at" or "note." He says, "Mark but," as if the thing he wants her to look at is not very significant. The "but" here means something like "only" here.
Indeed, in the second line, he explains that the smallness of the flea relates to the insignificance or triviality of the thing she has denied him.
Obviously she doesn't think the thing she has denied him is so trivial. The speaker's task in the poem, then, is clear: to prove that she's making a mountain out of a molehill by denying him what he wants.

It suck'd me first, and now sucks thee,
And in this flea our two bloods mingled be.

The speaker gets excited, and possibly aroused, by the thought that the flea that just bit him is now sucking her blood, mixing the two together.
We're sure there must be a name for a bug-bite fetish, but we don't know it. We hope that makes you think better of us.
Their blood is "mingling" like guests at a cocktail party. "Oh, hello, O-negative, I'd like you to meet B-positive."

Thou know'st that this cannot be said
A sin, nor shame, nor loss of maidenhead ;

A clearer picture is starting to emerge of what the speaker has been denied. It's a three-letter word that starts with an "s" and ends with an "x."
He is making a comparison between the mixing of "blood" – or other fluids – in the sex act with the mingling of the blood inside the flea. Sorry to get all anatomical here, but it's very much in the spirit of the poem.
Many of Donne's poems take the form of a long, complex argument, and we can see him starting to weave such an argument here.
He forces his companion to admit that no one would ever describe the mixing of blood inside an insect as a "sin," as "shameful," or as a "loss of maidenhead."
Let's start by thinking about things people in seventeenth-century England would definitely consider sinful and shameful. How about an unmarried woman sleeping with a dude who has a thing for bugs?
"Maidenhead" refers to virginity or chastity. Even if the woman is not technically a virgin, being promiscuous with the speaker could lead to a loss of her reputation as a "proper" maiden. These are no small stakes for the woman.
His argument, then, is that because the flea's fleshy meal is not shameful, sex with him must not be shameful either.

Yet this enjoys before it woo,
And pamper'd swells with one blood made of two ;
And this, alas! is more than we would do.

The speaker complains that the bug gets to enjoy her flesh without wooing her. No fair! The flea ("this") gets to do "more," erotically speaking, than either the speaker or the woman.
He almost sounds jealous of the flea, as if it were a romantic rival.
His tone is comically whiny, complete with an over-the-top, begging-for-attention "alas!"
The flea is "pamper'd" as he enjoys his luxurious feast of red, iron-rich goodness.
And, of course, Donne doesn't fail to give us the nausea-inducing image of the flea swelling up with blood as it continues to suck. We imagine the flea gradually expanding with a glazed look of satisfaction in its eyes.