The setting first presents the theme of loneliness. The novella begins a "few miles south of Soledad." Translated from Spanish to English, "soledad" means solitude. And although the landscape is populated with wildlife, there are no other humans other than George and Lennie. Because they have had to flee their last job (on account of Lennie's awkward encounter with a woman), they are alone once again. They do have each other but they are consistently running from job to job because this was the nature of itinerant ranch hands at that time, and because Lennie always got into some trouble; he and George had left previous jobs prematurely because of this.
George criticizes Lennie constantly but only to keep him out of trouble. George knows that without Lennie, he would have an easier time staying at a job, rather than being repeatedly cast out from jobs/society because of Lennie's innocent but dangerous social awkwardness:
"God, you're a lot of trouble," said George. "I could get along so easy and so nice if I didn't have you on my tail. I could live so easily and maybe have a girl."
But, since George has taken the responsibility of looking after Lennie, he must retreat from society with Lennie, whenever Lennie gets into some trouble or has trouble fitting in. The first chapter ends with another desolate and lonely description: a coyote (wild) howling up the river and a dog (tame/society) answering from the other side. At this point, George and Lennie are more like the coyote, away from society (in the wild).