A computer mouse with an adjustable palm rest includes a main housing defined with a longitudinal direction and a traverse direction and has a carriage. A connecting base is rotatably connected to the carriage along a first axis. A supporting casing has a front wall and a rear wall. A palm-resting cover is fixed to the supporting casing. The front wall is closed to the connecting base. The supporting casing is rotatably connected to the connecting base along a second axis. The supporting casing can be arranged at different oblique angles related to the connecting base. A positioner chain is formed on a surface of the connecting base or the supporting casing and has a plurality of positioning dimples. A positioning assembly abuts against one of the dimples and retains the supporting casing at one of the oblique angles related to the connecting base.