The central irony in The Plague lies in Camus' treatment of "freedom." The citizens of Oran become prisoners of the plague when their city falls under total quarantine, but it is questionable whether they were really "free" before the plague. Their lives were strictly regimented by an unconscious enslavement to their habits. Moreover, it is questionable whether they were really alive. It is only when they are separated by quarantine from their friends, lovers and families that they most intensively love them. Before, they simply took their loved ones for granted.

Camus' philosophy is an amalgam of existentialism and humanism. An atheist, Camus did not believe that death, suffering, and human existence had any intrinsic moral or rational meaning. Because he did not believe in God or an afterlife, Camus held that human beings, as mortals, live under an inexplicable, irrational, completely absurd death sentence. Nevertheless, Camus did believe that people are capable of giving their lives meaning. The most meaningful action within the context of Camus' philosophy is to choose to fight death and suffering.

In the early days of the epidemic, the citizens of Oran are indifferent to one another's suffering because each person is selfishly convinced that his or her pain is unique compared to "common" suffering. When the epidemic wears on for months, many of Oran's citizens rise above themselves by joining the anti-plague effort. The recognition of the plague as a collective concern allows them to break the gap of alienation that has characterized their existence. Thus, they give meaning to their lives because they chose to rebel against death. Fleeing the city or otherwise avoiding the anti-plague effort is tantamount to surrendering to the absurd death sentence under which every human being lives.

Just as any rebellion against death and suffering is ultimately futile, so do the anti-plague efforts seem to make little difference in the relentless progress of the epidemic. However, Camus' novel declares that this rebellion is nonetheless a noble, meaningful struggle even if it means facing never-ending defeat. In this way, The Plague is infused with Camus' belief in the value of optimism in times of hopelessness. Everyone who chooses to fight the plague, to rebel against death, knows that their efforts increase their chances of contracting the plague, but they also realize they could contract the plague if they did nothing at all. In the face of such a seemingly meaningless choice, between death and death, the fact that they make a choice to act and fight for themselves and their community becomes even more meaningful; it is a note of defiance thrown against the wind, but that note is the only thing through which someone can define himself.