The outbreak of SARS-CoV-2 virus forced office workers to conduct their daily work activities from home over an extended period. Given this unique situation, an opportunity emerged to study the satisfaction of office workers with indoor environmental quality (IEQ) factors of their houses where work activities took place and associate these factors with mental and physical health. We designed and administered a questionnaire that was open for 45 days during the COVID-19 pandemic and received valid data from 988 respondents. The results show that low satisfaction with natural lighting, glare, and humidity predicted eye-related symptoms, while low satisfaction with noise was a strong predictor of fatigue or tiredness, headaches or migraines, anxiety, and depression or sadness. Nose- and throat-related symptoms and skin-related symptoms were only uniquely predicted by low satisfaction with humidity. Low satisfaction with glare uniquely predicted an increase in musculoskeletal discomfort. Symptoms related to mental stress, rumination, or worry were predicted by low satisfaction with air quality and noise. Finally, low satisfaction with noise and indoor temperature predicted the prevalence of symptoms related to trouble concentrating, maintaining attention, or focus. Workers with higher income were more satisfied with humidity, air quality, and indoor temperature and had better overall mental health. Older individuals had increased satisfaction with natural lighting, humidity, air quality, noise, and indoor temperature. Findings from this study can inform future design practices that focus on hybrid home-work environments by highlighting the impact of IEQ factors on occupant well-being.