Background: Indoor air quality (IAQ) has a significant impact on human health. Since the COVID-19 pandemic began, more employees work remotely from home to reduce in-person contacts. This study aims to measure the difference in indoor air quality between the office and home environments and its impact on employees’ health. Methods: This was a pilot study conducted in McAllen, Texas, in two settings; 1) offices during January-July 2019 (pre-COVID-19) and 2) homes during June-October 2020. A total of eleven employees working in an academic organization participated in this study. The levels of particulate matter 2.5 µm (PM2.5), total volatile organic chemicals (tVOC), and CO2 were monitored in offices and households at multiple locations for a month. The frequencies of six symptoms of the Sick Building Syndrome (e.g., dry eyes) were evaluated at each period of monitoring. Results: In 82% of participants, the PM2.5 levels in households were significantly higher than those in offices (p<0.05). All households showed PM2.5 levels greater than the annual mean standard (10 ug/m3), while 82% of offices showed levels in compliance with it. The tVOC and CO2 levels were all below the guideline. Among 9 subjects who completed both health surveys, 7 subjects reported the changes in health outcomes in accordance with different PM2.5 levels between those two periods. Conclusions: This study showed that working from home during the pandemic may pose more health concerns for employees due to the poor indoor air quality. The interventions to improve the home IAQ and health outcomes should be considered.