In their own individual ways, Candy, Crooks, and Curley's wife are outsiders on the ranch and in society as a whole. It is because of their outsider status that they are isolated and lonely.
Candy is an outsider on account of his disability. An old man with only one hand, Candy is acutely aware of his condition, and is constantly preoccupied with the thought that he will soon be fired. Inevitably, this makes him feel different from the other workers at the ranch, who at least have sufficient health and youth to be able to change their destinies. Candy's condition also provides the spur for him to jump at the chance to be part of George and Lennie's dream of owning their own ranch.
Crooks is also lonely and isolated. As the sole Black man on the ranch, he's set apart from the others quite literally, forced to live in his own little shack. Crooks confesses that he's lonely, but given the predominant racial prejudice of the age, there's nothing he can do about it. He can engage in superficial conversation with the other men, but that's about as far as it goes. The racial barriers between himself and the others are simply too great for him to be able to forge meaningful connections with the guys in the bunkhouse.
As the only woman on the ranch, Curley's wife is about as lonely and as isolated as it's possible to be. Though much better off than Candy, and with the white privilege denied to Crooks, she's still all alone in the world. Trapped in a marriage that seems less than happy, and with unfulfilled dreams of movie stardom, Curley's wife is so lonely that she often hangs around the ranch hands, engaging in conversation and sexually provocative behavior.