In Of Mice and Men, Curley’s wife and Crooks represent loneliness and isolation in terms of gender and race, respectively. Curley’s wife also symbolizes dependence through her idleness. She does not even have a name, is the only female person on the ranch, and does not have a job to do. Wholly dependent on her vain, insensitive husband, she wanders around the ranch. The refuge she sought in marriage, to a man she has just met, does not fulfill her desire to escape her humdrum life. Her loneliness drives her to confide in Lennie, leading him to the fatal error of believing they are friends.

Crooks, in contrast, is a hard-working man who lives apart from the other ranch hands because of his race. The ranch living accommodations are segregated so he cannot bunk with the other hands. However, this separation also gives him a measure of privacy that the others lack and that he values. This aloofness is accentuated when Lennie walks in uninvited; Crooks tells him that he “ain’t wanted,” just as Crooks himself is not wanted, “Because I’m black.”

Steinbeck wrote “Of Mice and Men” during the 1930s at a time when significant social and economic problems where arising, prompted by the Great Depression, which forced the general workforce of America to become itinerant workers. As a result the characters of the novella live limited existences dominated by the loneliness of a repetitive cycle of earning a large enough “stake” so that they can spend it in a “cat house”, where they can drink “whisky” and “play cards”.

Crooks is excluded from the rest of society in his own “bunk” as a result of the oppressive violence and prejudice he has been the victim of. Experiencing such a plight has resulted in him retiring behind a façade of aloofness. This can be seen by the proud way in which he takes care of his bunk, “the room was swept and fairly neat”, in stark contrast to the bunk houses of the other ranch workers. When actually faced with the presence of others, Lennie and Candy, he gains a large amount of self confidence, which encourages him to try to counter the intrusion of Curley’s Wife, “you got no call foolin’ aroun’… causin’ trouble”. Of course, this is highly out of character and it demonstrates how unusual it is for him to find himself in the company of others.

Similar to Crooks, Curley’s Wife also experiences extreme exclusion from society. However, in her case, it is her gender and her husband that are the obstacles in her search for companionship. This is because, as was the characteristic prejudice towards women at that time, the other characters are suspicious of her and they fear that because of her they might “get canned”. Consequently, she is attracted to Lennie and she devises a complex arrangement to ensure that she could safely be alone with him in the barn. When she gets the chance to talk to him, the words pour out of her in a “passion of communication”. In addition, the interaction reveals a compassionate side of her, which her separation was concealing, when she consoles Lennie after he has killed the puppy, “don’t you worry non’”.

The whole novel Of Mice and Men is filled with lonely characters.  Candy is lonely as an old man with no family and no secure future.  George is lonely for companionship because he takes care of Lennie and because he is a migrant worker and never has the time to cement friendships or relationships.  Curley and his wife are alienated from each other, and Curley from the whole ranch it would seem.  Crooks is physically lonely, as no one socializes with him, and there is no one else from his race or culture to socialize with.

Curley's wife and Crooks do not, by themselves, then, symbolize loneliness.  Rather, the whole novel portrays the all-encompassing loneliness of a broken society in the depths of the Depression, and of those who are most vulnerable in it.  This includes Curley's wife and Crooks, but it also includes almost everyone else in the story.

I do think they are both symbols of loneliness in one simple way: they are each a representative of an under-represented social class.

Curley's wife is the only woman in the entire novel who has a speaking part. Look at her name! She doesn't even receive an identity of her own. I think this shows that she represents an independent or individual or isolated experience.

Crooks, likewise, is the only black man on the ranch. He has to deal with being separated from the rest of the men because he smells different. He even physically has a different sleeping location. He too is isolated, representing loneliness. 

Are you sure that there is supposed to be anything beyond the simple fact that they are really lonely and act really lonely?  I do not really think they are supposed to symbolize anything -- at least not in the way that the farm that Lennie and George dream of symbolizes freedom or Candy's dog represents what happens to people who outlive their usefulness.

To me, Curley's wife and Crooks just ARE lonely, as you say.  They show how loneliness affects people -- Crooks tries to destroy Lennie's dream even though he really wants to share in it, Curley's wife acts in ways that will get the men in trouble even though she really wants their company.  But I do not see them as symbols.  I see them more as characters who are defined by their loneliness.