This is no sprawling, Dickensian novel with multiple plots and characters moving all over London. The setting is almost as small and confined as the plot; it occurs over a period of three days in four specific locations: a wooded area next to the Salinas River, a bunkhouse on the ranch, the stable hand's room on the ranch, and the main barn on the ranch. In fact, it's so tightly constructed that it could easily be a play. (Check out "Symbols: Morality Play" for more on the way Of Mice and Men might be like a play.)
But there is a larger background to the novel's setting: the Great Depression, which left people all over the country (especially men) poor and desperate for work. This poverty makes the characters suspicious and distrustful: there literally isn't enough to go around. Against this backdrop of suspicion and isolation, Lennie and George's friendship seems even more remarkable—and even more doomed.