During the Great Depression, conditions were very harsh for Americans. Because there were few jobs, many men became dispossessed as they were forced to leave their homes and ride the rails in search of work. They were also disenfranchised because with so many men out of work, these migrants were compelled to take whatever jobs they could.
Some, like Crooks, are further marginalized because of race, and Lennie is not included in some activities because he is mentally challenged. Curley's wife is representative of those women who dream of leaving their small community and becoming an actress or some position from which they gain attention, but who go nowhere, just trading one kind of misery for another. Nearly all feel alienated and lonely.
Like so many others, George and Lennie have little; they carry bindles which hold all that they own in the world. They have come to the Salinas Valley where it is harvest time in order to procure positions as laborers. Although Lennie is mentally slow, he has brute strength and can do the work of nearly two men. However, other bindle stiffs ridicule Lennie, and women toy with him without realizing the potential danger involved because Lennie does not know his own strength. Consequently, the flirtatious women end as victims of Lennie's strength, and George and Lennie must go on the run, abandoning their work. But, they are more fortunate in that they have each other, whereas most men are alone.
Crooks expresses this terrible alienation from other men when the ingenuous Lennie talks with him and stands in Crooks's room: "Guys don't come in a colored man's room much." But, Lennie continues, anyway, so Crooks tolerates him; then, he asks Lennie how he would like to have to stay out there as he does all by himself. He declares,
"A guy needs somebody--to be near him. A guy goes nuts if he ain't got nobody."
The old swamper, who has lost a hand in an accident on the ranch, worries that he will become too old and be sent away or left to die like his old dog who outlived his usefulness and who Candy had one of the other men shoot. Candy is without hope until he hears George mention that he and Lennie are saving to buy some land. Then, he asks to join in on their venture, offering the money he was given for his accident. For the first time, George contemplates their "dream" as a real possibility.
With the entry of Curley's wife into the barn in Chapter 4--alienated herself as the sole female on the ranch--the men become ill at ease because Curley is irrationally jealous. She becomes an Eve, a temptress, who disturbs the fraternity of the men bonded in the dream of owning a place together. Further, with her accidental death at the hands of Lennie, Curley's wife destroys all hopes and Lennie loses his life, leaving George alone and the dream of a farm dead for him and old Candy.
The losses of family and friends are probably the greatest ills, the greatest unfairness, to have come out of the society in which the characters of Of Mice and Men find themselves. Forced to live in confined areas among strangers, the men in the bunkhouse and Crooks, who is further isolated, feel edgy and deprived of any privacy. When Curley's wife comes into scenes, she, too, is lonely; however, her loneliness works against herself and the men because she is "jail bait" and possible trouble with the son of the boss, her husband.
Certainly, the conditions of society during the setting of Steinbeck's novella are anything but conducive to fairness, harmony, fellowship, friendship, and hope. It is a time in society throughout the country during which "the best laid schemes o'mice an' men" fade into despair and the social miasma called the Great Depression.