Objective To explore the mental health status of rural residents in Southwest Anhui province and its influencing factors during the coronavirus disease 2019 (COVID-19) epidemic. Methods A total of 766 rural residents in Southwest Anhui province completed the self-made general information questionnaire and symptom checklist 90 (SCL-90) online from Feb. 1 to Feb. 5, 2020. The mental health status was compared among the residents with different demographic information. Multivariate logistic regression analysis was used to screen the influencing factors of mental health. Results A total of 887 online questionnaires were sent out, and 766 valid questionnaires were collected, with an effective rate of 86.4%. The incidence of psychological problems in the rural residents in Southwest Anhui province was 23.3% (178/766) during the COVID-19 epidemic. The main manifestations were compulsion (15.1%, 116/766), interpersonal sensitivity (9.0%, 69/766), and sleep and diet problems (8.5%, 65/766). All factor scores of SCL-90 of the rural residents were lower than the national norm, and the scores for somatization, compulsion, interpersonal sensitivity, depression, anxiety, hostility, paranoia, psychotic, and "other" factors were significantly different from the norm (all P<0.01). Multivariate logistic regression analysis showed that age (odds ratio[OR]=0.977, 95% confidence interval[CI] 0.965-0.989), education level (OR=0.693, 95% CI 0.497-0.966), family structure (OR=1.934, 95% CI 1.223-3.059) and the knowledge about the epidemic (OR=0.948, 95% CI 0.914-0.983) were the influencing factors of mental health (all P<0.05). Conclusion During the COVID-2019 epidemic, the mental health of the rural residents in Southwest Anhui province is good. It is important to pay more attention to the susceptible population and further popularize the knowledge about COVID-19 epidemic and maintain good mental health of rural residents during the epidemic.