Background: Although adopting a neutral sitting posture is recommended to avoid potentially painful positions, many sitting postures are still adopted in daily life. Few studies have examined the effects of sitting postures in daily life, such as the right cross-legged sitting posture and the left cross-legged sitting posture. Ob-jectives: (1) to determine how personal characteristics, including gender, age, and BMI, influenced muscle activity when operating a computer mouse in sedentary people.; (2) to investigate the effects of asymmetric sitting postures on neck and back muscular activity, and to evaluate the differences in the right and left muscular activities in the neck and back during a computer mouse task in sedentary people. Methods: A 3x3x2 (Backrest x Lower extremity x Right-left difference of examined muscles) repeated experiments design was used. The activities of four muscles (the trapezius and erector spinae on both sides) were collected by surface electromyog-raphy. Sixty sedentary people were recruited and randomly assigned sitting postures. Results: The trapezius activity was higher in males than in females, and higher in the overweight group than in the healthy and underweight groups. The trapezius ac-tivity was lower in the left cross-legged sitting posture than in the symmetric sitting posture. The erector spinae activity was higher in the right side than in the left side in both the left and the right cross-legged sitting postures. Conclusion: The com-pensation mechanism of lower trunk and pelvis regions was found in asymmetric sitting posture. Therefore, asymmetric sitting postures are not appropriate options for sedentary people.