The 57-year-old comedian paid tribute to Cleto, the leader of the Jimmy Kimmel Live! house band Cleto and the Cletones, during his opening monologue on Tuesday night's show, and admitted his pal's passing is "just not fair".
He opened the show by saying: "We've been on the air for almost 23 years and I've had to do some hard monologues along the way, but this one's the hardest because late last night, early this morning, we lost someone very special who was much too young."
Kimmel then recalled his lifelong friendship with Escobedo when they grew up in the same street in Las Vegas.
He added: "Everyone loves Cleto ... everyone here at the show.
"We are devastated by this. It's not … It's just not fair.
"He was the nicest, most humble, kind and always funny person.
"There is no one in my life I felt more comfortable with."
Escobedo's dad, Cleto Escobado Sr, who plays the tenor and alto saxophone in the Cletones, performed with the band on Tuesday night's episode, and Escobedo's mother was in the studio audience.
But Kimmel confirmed the show will not air on Wednesday or Thursday following the star's passing.
He said: "We're going to take the next couple of nights off."
And he revealed the show went ahead on Tuesday because Escobedo would've wanted it to continue due to Eddie Murphy being a guest.
Kimmel also paid tribute to Escobedo on Instagram, remembering his pal as "a great friend, father, son, musician and man".
He wrote: "Early this morning, we lost a great friend, father, son, musician and man, my longtime bandleader Cleto Escobedo III. To say that we are heartbroken is an understatement. Cleto and I have been inseparable since I was nine years old. The fact that we got to work together every day is a dream neither of us could ever have imagined would come true. Cherish your friends and please keep Cleto's wife, children and parents in your prayers."
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