Objective To study the characteristics of mouse-desktop and wrist-desktop contact pressure distributions during different mouse operations, and investigate the influence of desktop on the mouse and wrist during mouse operations, so as to obtain biomechanical references for musculoskeletal disorders of the hand and wrist. Methods The laser scanner and TekScan pressure measurement system were employed to measure contact area and contact pressure of the mouse and wrist during different mouse operations. Results The contact pressure, contact area, and contact force varied with time, and the peak contact pressure of the mouse and wrist with desktop were obtained. The peak contact pressure of the mouse in single clicking of left, right key and scrolling of middle key was 62.87, 33.83, 74.66 kPa, respectively, and for the wrist, the minimum contact pressure appeared in key clicking, being 23.25, 11.02, 16.26 kPa, respectively. Conclusions During mouse operations, the thenar, hypothenar as well as the ulnar and radial sides of the wrist are persistently subjected to the continuous pressure, therefore, repetitive and continuous mouse operation can lead to the development of carpal tunnel syndrome of wrist or other MSDs.