Of Mice and Men is replete with examples of loss. In fact, most, if not all, of the characters have experienced loss in the past or experience it in the course of the novella. Additionally, some of these losses add to the bigger theme of the unattainable American Dream.
The first example of loss can be seen with Candy and the death of his dog. When Carlson insists on shooting it because he "stinks," Candy responds, "I had him so long. Had him since he was a pup. I herded sheep with him." Through his persistence, Carlson finally gets the okay to kill the animal, leaving Candy on his bed, rolled over facing the wall and silent. He has ultimately lost his only friend and companion in an already lonely ranch.
Later, in chapter 5, we learn that Curley's wife once had the hope of becoming an actress but lost that dream when her mother made it impossible for her to achieve it. She indicates to Lennie that a man she once met "said he was gonna put (her) in the movies." When this didn't happen, her desperation to get out of her mother's home led her to ultimately marry Curley the same night she met him. Now that she's trapped on the ranch and has forever lost the opportunity to become an actress, she goes on to list all of the things she could have done if she had succeeded, such as had nice clothes, gone to movie previews, and "sat" in hotels, all losses in her book.
Finally, at the end of the novel, Candy and George both realize that, with the death of Curley's wife, they have lost their chance at the American Dream, their farm. Candy asks, "You an' me we can get that little place, can't we, George?" He soon answers his own question. "Candy dropped his head and looked down at the hay. He knew."