The coronavirus disease-2019 (COVID-19) pandemic has brought huge and continuous damage to mental health. The mental health of non-medical college students after returning to school remains largely unknown and the influencing factors were awaited to be deciphered. This cross-sectional study was launched among 1,083 non-medical students in Zhanjiang city by means of online survey (WeChat App) from August 1st, 2022 to August 7th, 2022. Knowledge about COVID-19 and attitude toward COVID-19 were assessed by using 7-items and 5-items questionnaires, respectively. Sleep quality, anxiety and depression symptoms were evaluated by Pittsburgh sleep quality index (PSQI), Hamilton depression rating scale-17 (HDRS-17) and self-rating anxiety scale (SAS), respectively. The results showed that more than half of the participants were knowledgeable about COVID-19. The majority of the participants held positive attitude toward COVID-19. The data demonstrated that 6.8% students had poor sleep quality, and 1.86, 0.37 and 0.37% students had mild, moderate and severe anxiety, respectively. About 26.7, 4.7 and 1.7% students had minimal, mild–moderate and severe depression. Female students showed higher proportions of anxiety (p = 0.02) and depression (p < 0.0001) than male students. Students with monthly household income below 3,000 RMB were more vulnerable to anxiety (p = 0.017) and depression (p = 0.004). Correlation analysis and Multivariate logistic regression analysis results showed that lower grade was positively related with anxiety and depression. Female students, income lower than 3,000 RMB/month, poor knowledge about COVID-19 and negative attitude toward COVID-19 were associated with insomnia, anxiety and depression. This study indicated that during the COVID-19 pandemic, a majority of non-medical students returning to school remained good sleep quality and a small number of students suffered from depression and anxiety. To our knowledge, this is a novel study revealing the mental health of non-medical college students concerning COVID-19 in Zhanjiang.