Objective: Primary care physicians (PCPs) play a key role in responding to the COVID-19 epidemic. The objective of this study was to explore the influencing factors associated with self-reported psychological distress among a sample of PCPs in China in relation to COVID-19. Methods: An online survey was distributed to a sample of PCPs in Chengdu city between February 10 and February 13, 2020. The survey consisted of three sections: demographic characteristics, COVID-19-related questions, and the General Health Questionnaire-12 (GHQ-12). After 5 months, a follow-up survey investigating the change of the GHQ-12 was conducted. Results: A total of 712 PCPs completed the baseline survey (11.8% of those invited), 55.6% were female and 74.4% were aged between 30 and 49 years. High levels of psychological distress (GHQ-12 ≥3) were observed in 29.2% and were associated with low preparedness, high work impact, working with infected residents, personal life impact, and concerns, as well as older age and being married (p values < .05). Logistic regression analysis showed that psychological distress was associated with low preparedness (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.87-0.96), high work impact (OR = 1.11, 95% CI = 1.03-1.20), personal life impact (OR = 1.12, 95% CI = 1.07-1.17), and safety-related concerns (OR = 1.09, 95% CI = 1.02-1.16). At the 5-month assessment point, high psychological distress was less frequent (21.8%). Conclusions: COVID-19 has resulted in high levels of distress in approximately 30% of PCPs in China. Factors associated with high psychological distress levels include low preparedness and high levels of work impact, personal life impact, and concerns. These findings highlight the importance of enhancing psychological health throughout the course of infectious pandemics.