Mathis bruised his thumb while blocking a pitch on Sept. 9 against the Braves.
An initial X-ray came back negative, and Mathis returned to the lineup on Sept. 16. He tried to play through, and he appeared in seven more games before feeling more discomfort.
A second X-ray was taken after he came out of the game on Sept. 24, and a fracture was detected.
"His season is over," manager Mike Redmond said.
Mathis missed the first month of the season with a right collarbone fracture.
Mathis appeared in 73 games, and he batted .181, with five home runs and 29 RBIs.
Koyie Hill started at catcher on Friday night against the Tigers, and Rob Brantly is the other healthy catcher on the roster.
Also on Friday, it was announced that rookie outfielder Jake Marisnick will be undergoing a scope on his left knee, so his season is over.
The 22-year-old rookie outfielder opened the season at Double-A Jacksonville, and he was called up in late July. Initially, he started a majority of the time in center field. But he began to slump, and in 40 games and 109 at-bats, he ended up hitting .183 in the big leagues. He batted .280 in the Minors with 12 homers and 46 RBIs.