George’s loneliness is due to his loyalty to Lennie, his line of work, and independent nature. George often tells Lennie how his life would be different if he did not have him as burden: "I could get along so easy and so nice if I didn't have you on my tail. I could live so easy and maybe have a girl." (p. 8). George is a migrate worker and therefore switches jobs often, making it hard to build relationships. Because of Lennie and the trouble he causes, the two men have to move even more than other workers: "You can't keep a job and you lose me ever' job I get. Jus' keep me shovin' all over the country all the time." (p. 12). George’s loneliness also binds him to Lennie – their friendship is the only constant relationship in his life. Their friendship is in great contrast to the distrust he displays towards others. He dreams of having a ranch for the two of them to settle down on, and live their life simply.
Candy is an older man who lives on the ranch George and Lennie work at. He has lost his hand while working there, so is offered a permanent job as compensation. He has no family, and the people on the ranch are constantly changing around him. Because of his handicap, he doesn’t work with the other men on the ranch, and is often excluded. Due to this he clings to his old dog that he keeps for company, and is very eager to please others. He describes almost everyone as a “nice fella”, and avoids conflict. He hopes to find security and companionship by joining in on George’s and Lennie’s dream to have their own ranch.
Curley’s wife has no name, and is only seen as the possession of her husband and the temptress of the ranch. As the only woman on the ranch, she lacks company and people to talk to, and is seemingly dissatisfied with her life. Her husband Curly is jealous and possessive, so other men do not dare talk to her in fear of getting Curly’s wrath upon them. She dresses provocatively and flirts with the ranch hands to get attention, and most probably to infuriate her husband. "Married two weeks and got the eye? Maybe that's why Curley's pants is full of ants”, George says about her (p. 31). Curly’s wife is bitter about the past and sad about her lost potential – she tells Lennie that she could have been a movie star, had her mother not intervened. Her loneliness and craving for spotlight cause her to be self-obsessed, and that eventually leads to her death.
Crooks is the stable-hand, named after his crooked back. He lives on his own in the stables, as he is the only black man on the ranch. Due to the racial prejudice on Californian ranches, he is treated as an outsider, and separated from the others. Living in loneliness has given Crooks a mean streak, as is seen when he suggests to Lennie that George won’t come home, just to pick on him. Crooks also gets caught up in the dream of George’s and Lennie’s, hoping to be able to work on their dream ranch.
Though the characters of Of Mice and Men are surrounded by other people, they all are isolated. The characters confessing their loneliness to strangers shows their desperation. All of them search for companionship, but it seems to be unattainable in the world of migrant workers.