There are several "bad guys" in this story, starting with the village doctor. He is so corrupt he even makes the baby Coyotito sick to appear as a lifesaver and then get more money. The disease of greed spreads (as the evil song from the pearl), corrupting even the priest, who can't help but think of how the church might profit from Kino's sudden fortune. And so it goes with the merchants of the town and then the pearl buyers, who go in collusion against Kino to break the price of the great pearl well below its market value. Finally, the posse tracks down Kino and his family much as hunting animals, and in the flight Coyotito is killed. It is only when Kino hurls the pearl back into the bay that the spell of greed and corruption over the village is broken.

Note that although the pearl is sometimes personified, it is not considered an antagonist itself; evil is rather spawned (as a pearl in an oyster) within the recesses of the heart.

The antagonist of the story consists of the power structure the Spanish have established against the native population. This includes the doctor, who will only treat Kino's son if he has money, the pearl buyers and the other people who try to steal the pearl. They are all connected in their desire to cheat Kino out of the full value of the pearl. Because Kino chooses to act alone, he cannot stand up to the power structure that exists in his town.