There are several possible themes for this story, depending on which aspect you choose to emphasize. The most obvious would probably be "Death is inevitable; you can't escape, no matter how wealthy or powerful you are." We see this with Prince Prospero and his partygoers, of course. His desperate attempt to cheat Death, and his willingness to revel in celebration while others are dying, ends with his own submission to the Red Death. Thus, he falls victim to the one thing he tried to escape.
Another theme (closely related) is that we are all subject to the passing of time. In the story, time is closely linked to death, as each tick of the clock forces the partygoers to consider their own mortality. Indeed, the clock stops striking after the last eprson has died. Thus time becomes a symbol for unstoppable forces, the ones no one can escape.
There are several themes in "The Masque of the Red Death". The central theme is that no man escapes death. The other central theme is that time passes no matter what one might attempt to do thereby causing death to come no matter what.
The other theme is madness or insanity. It is insane to have a ball in the middle of the plague ravaged country. Prince Prospero may be the narrator of the story, and as such may also be the madman. Poe is the genius of the disturbed interior monologue. The ball may simply be a figment of the disturbed mind of a madman.
At the stroke of midnight, the partygoers are confronted with a newcomer to the party. This person is costumed in such a manner that he appears to be a victim of the "red death" a type of plague that causes bleeding from the pores of the body. One might now call it a type of Ebola virus based on the symptoms given in the story. The partygoers have not escaped the red death, it has come to visit them.
The passage of time is also noteworthy as each of the guests pause as the clock strikes the hour proving that they have escaped death and this plague for a measurable period of time. They breathe a sigh of relief and return to their revelry. This works until midnight when a previously unnoticed guest arrives clad in the death robes and smeared with blood. This costume is so like the appearance of a victim of the red death that Prince Prospero and the guests are shocked and then angered. However, the guest is the red death. The guests have not escaped the plague, and time stops for each one of them as they die.