The central relationship in "Of Mice and Men" is between George and Lennie. Despite the emotionally rich and satisfying relationship between these two characters, the relationship also draws attention to their essential loneliness. Early in the novel, George tells Lennie that their job, that of a migrant farm worker, is the loneliest in the world. While George is intelligent and well aware of his own loneliness and low status in life, Lennie has a learning disability that leaves him somewhat unaware of his status. When Lennie dies, George is again left alone.
When Lennie and George arrive at a ranch for work, they meet Curley, the son of the owner of the ranch, and his wife, who flirts with the farmhands despite her husband's jealousy. Curley's wife is unhappy in her marriage and feels trapped on the ranch; she tries to make connections with other people, but her behavior causes problems for herself and the farmhands.
Candy is an elderly farmhand whose only companion is a sick, old dog that the other farmhands encourage him to shoot. Candy's loneliness keeps him from shooting his dog; he has no other connections in the world aside from the dog and can't bear to lose it. Later in the novella, after his dog is shot, he joins up with Lennie and George in their scheme to buy a farm and somewhat relieves his loneliness.
Crooks is an African-American farmhand whose loneliness comes from his isolation from the larger group due to his skin color. Crooks is one of the most lonesome characters in the novella, as he is kept separate because of racism and therefore cannot make a strong connection with others.