"Pox On't" (which encompasses several variations, including "pox on'em" and "pox upon him") is an idiom that a few of the characters repeat throughout the play. Used a few dozen times by the Cavaliers, especially when things don't go their way with women or money, this moderate curse highlights their masculinity and ruggedness. In this way, the phrase emphasizes the favors, relationships, and exploits that the men feel they are owed.
In this idiom, the speaker wishes pox upon whoever or whatever they are cursing. "Pox" could mean either smallpox or "the great pox," which people called syphilis at the time. Knowing Willmore, Blunt, and Frederick—and their lewd manners of speaking—one can safely assume that they have venereal disease on their minds. Thereby, when a character says "pox on't," he is literally saying "I would like to give that person or thing syphilis." However, swear words are often idiomatic, as they contain an intended figurative meaning that is common knowledge among native speakers of the language. When reading or watching the play, Behn's contemporaries would know what this moderately vulgar but nonetheless common phrase meant. If the idiom sounds familiar, it might be because it is featured in a famous line spoken by Mercutio in Romeo and Juliet, in which he wishes "A pox on both [their] houses" before he dies.