Quarantine policies during the coronavirus disease 2019 (COVID-19) pandemic prolonged time spent at home, leading to an unintended occurrence of sick building syndrome (SBS) symptoms. The aim of this study was to investigate the prevalence of SBS symptoms among residents in Suzhou, China, during the COVID-19 pandemic. A questionnaire survey was conducted online from February to May 2022. A total of 442 adults were included in this study. The prevalence of SBS symptoms was much higher during the COVID-19 pandemic, and the proportions of general, mucosal, and skin symptoms were 59.3%, 45.5% and 49.1%, respectively. The influences of building characteristics, occupant lifestyle, indoor environment and perception of indoor environment were analysed using a multivariate logistic regression model. Neighbourhood pollutant sources, older residences, non-ownership and humidity indicators were significant risk factors for SBS symptoms. Frequent use of air fresheners was significantly associated with general (adjusted odds ratio (AOR): 4.9, 95% confidence interval (CI: 2.4–10.0), mucosal (AOR: 5.3, 95% CI: 2.4–11.5), and skin symptoms (AOR: 4.6, 95% CI: 1.6–13.1), while the use of disinfectants was significantly correlated with skin symptoms (AOR: 4.0, 95% CI: 1.5–10.7). Residents’ perception of an uncomfortable indoor environment was a significant predictor of general (AOR: 2.2, 95% CI: 1.2–4.0) and mucosal symptoms (AOR: 3.1, 95% CI: 1.6–6.0). The use of air cleaners can reduce the prevalence of general symptoms. An important finding of this study is that the psychological impact of staying at home for a long time was associated with general symptoms (AOR: 1.3, 95% CI: 1.1–1.7), which means that attention should also be paid to the mental health of residents during the COVID-19 pandemic. Although the quarantine period has now ended, our results can still serve as a reference for the impact of the indoor environment on the health of people with SBS, especially for those who stay at home for a long time, such as the elderly.