Obsessive love versus real love
Florentino's love for Fermina is intense and lifelong, but it is also self-constructed. He loves an idea of her more than the actual person. The novel puts that kind of love next to the Urbino marriage, which is messier and more mutual, and lets the reader compare them.
Time and aging
The novel spans more than fifty years and ends with its characters in old age. Garcia Marquez shows that desire does not stop when bodies age, but it does change shape. The late-life romance between Florentino and Fermina carries weight precisely because both characters have lost so much already.
Love as illness
The title is not ironic decoration. Garcia Marquez draws a sustained parallel between cholera and lovesickness. Both produce physical symptoms, both spread without warning, and both can be fatal. The cholera flag at the end ties the metaphor to the plot directly.
Class and social ambition
Fermina's father rejects Florentino because of his social standing. Fermina marries Urbino partly because he represents stability and status. Class shapes every major relationship in the novel, even when the characters pretend it does not.
Self-deception
Florentino tells himself he has been faithful. He has not. Fermina tells herself her marriage was purely practical. It was not. Garcia Marquez builds the novel around characters who misread their own lives, and the reader sees the gap between what they believe and what actually happened.