Objective: Evaluate the effects of 10 min/day of yoga for 1 month on musculoskeletal discomfort and mood disturbance of home-office workers. Background: The COVID-19 pandemic forced many people to switch to teleworking. The abrupt change from an office setting to an improvised home-office may negatively affect the musculoskeletal and emotional health of workers. By providing mental and physical exercises, yoga may be effective in reducing adverse effects. Method: Fifty-four participants (42 women, 12 men) followed a 1-month yoga program, while 40 participants (26 women, 14 men) continued with their common work routine. The Cornell Musculoskeletal Discomfort Questionnaire was used to evaluate severity, interference with work and frequency of pain, and to obtain a total discomfort score for 25 body areas. Mood disturbance was evaluated with the Profile of Mood States questionnaire. Both groups completed both questionnaires, before and after the experimentation period. Results: After 1 month, for the yoga group only, significant reductions were observed in the discomfort of eyes, head, neck, upper and lower back, right wrist, and hips/buttocks, as well as reductions in discomfort severity, frequency and interference for the neck, upper and lower back. Total mood disturbance was also significantly reduced for the yoga group only. No favorable changes occurred for the control group. Conclusion: The yoga intervention program appears to reduce musculoskeletal discomfort and mood disturbance of home-office workers. Application: Sedentary workers may benefit from 10 min/day of yoga during the workday to attenuate potential physical and emotional discomfort during the current pandemic and beyond.