As is so often the case, the title of a work initiates the tone, or mood, of the narrative.  John Steinbeck's title's allusion to the poem of Robert Burns about the plough's destroying a little mouse's winter nest connotes the disorder of America during the Great Depression, the despair, and "quiet desperation" of lives, especially those of the itinerant worker.

I'm truly sorry man's dominion
Has broken Nature's social union,
An' justifies that ill opinion
Which makes thee startle
At me, thy poor, earth born companion
An' fellow mortal!....

But Mousie, thou art no thy lane,
In proving foresight may be vain:
The best-laid schemes o' mice an' men
Gang aft agley, [goes awry]

Just as the plan for the future of the mice has been destroyed, so, too, do the "best-laid schemes" of George, Lennie, and Candy "go awry." For, the forces of an indifferent universe of Naturalism exist in the world of the itinerant worker. Such forces as the accident of Candy, the mental debility of Lennie, and the inability of George to control Lennie against the seductive powers of Curley's wife obstruct their happiness.

Here are examples of the desperation of the lives of the men in Of Mice and Men

• The old swamper finds himself disabled and likely to be fired if he is not considered useful.  Like his dog that nature has rendered useless because of his age, Candy feels the threat of helplessness and death:

"They'll can me purty soon.  Jus' as soon as I can't swamp out no bunk houses they'll put me on the county."

• Having nearly escaped a lynching in Weed, George is always anxious that Lennie will do something wrong that will endanger their lives.  So, he constantly instructs Lennie not to talk or to leave "jail bait" alone. Nevertheless, Lennie incurs danger when he defends himself against Curley, inciting the wrath of Curley. Also, when he sits in the barn with Curley's wife, like the mouse of Burns's poem, George's well-laid plans "go awry" as Curley's wife is inadvertently killed by his uncontrollable hand strength.
• Lennie knows that he needs George. So, when Crooks taunts him by saying that George may not return from town, Lennie becomes distraught; angered, he scolds,

Lennie growled back to his seat on the nail keg. "Ain't nobody goin' to talk no hurt to George."

• After Lennie inadvertently chokes Curley's wife, he runs to the clearing where George has instructed him. However, he imagines the voices of order scolding him in the image of his aunt and that of the rabbit.  

Lennie moaned with grief...."I might jus' as well go away. George ain't gonna let me tend no rabbits now."

The rabbit repeated...."He gonna leave you, ya crazy bastard...."

Lennie put his hands over his ears.  "He ain't, I tell ya he ain't."  And he cried, "Oh! George--George--George!"

Indeed, with the death of Curley's wife and the death of the dream of owning a ranch, the lives of Lennie, George, and Candy are certainly ones of desperation.  Thus, the overall mood of Of Mice and Men is a dark and pessimistic one in which the men are but pawns of an uncaring world.