In the very beginning of the story, we learn from the setting which is set in town of Soledad, meaning loneliness. So, the tone is sad, doomed, helpless and tragic.
Mostly, the tone of this novel is honest, sympathetic and realistic. Steinbeck seems sympathetic towards his characters, however he is not going to bring a happy conclusion for them. He shows contrasts of real world of limited sources, poverty, human intolerance, limiting social roles with the dream world of autonomy, wealth, freedom and friendship.
Let us take example of Lennie, who has a kind of mental disability that influences his moves and actions. Although he commits a dreadful crime, yet Steinbeck presents him in a way that make the readers hesitant to judge him. He portrays them as they are, and do not insists that readers think this or that way. He presents them as human beasts, facing inevitable suffering of their existence.