Objective: The present study aims to assess the mental health of Chinese people during the Omicron variant outbreak in March 2022. This study also explores how coronavirus disease 2019 (COVID-19) exposure history, vaccination status, sleep quality, and alcohol dependency symptoms influence mental health outcomes. METHODS: The data were collected from 1049 Chinese people through Tencent using a structured questionnaire utilizing convenience sampling technique. The online cross-sectional study included the Chinese version of the Depression, Anxiety and Stress Scale 21, the Alcohol Use Disorder Identification Test, Fear of COVID-19 Scale, Warwick Edinburgh Mental Well-being Scale, and Pittsburgh Sleep Quality Index to assess depression, anxiety, stress, alcohol dependency, fear of COVID-19, and sleep quality, respectively. Statistical analyses included independent sample t-tests and χ2 tests to assess the differences in study variables across demographic characteristics, and multiple linear regressions to assess the effect of the experience of COVID-19 infection, vaccination, and mental health variables on sleep quality and alcohol dependency. Results: Results showed that 11.5% to 32.4% of the participants had a poor mental health symptoms. Males had significantly higher depressive symptoms (χ2=12.283, df=4, P=.015) and alcohol dependency symptoms (χ2=66.604, df=3, P < .001), and females had significantly lower mental well-being (χ2=12.742, df=2, P=.002). Additionally, findings showed that stress (β=.250, P < .001), mental well-being (β=-.166, P < .001), and fear of COVID-19 (β=.061, P=.029) predicted poorer sleep quality, and anxiety (β=.115, P=.035) and mental well-being (β=-.097, P=.002) predicted alcohol dependency symptoms. Conclusion: Since the pandemic-induced mental health challenges persist for a prolonged period, the findings of these relationships offer guidance for mental health professionals to formulate therapeutic interventions to help people cope with psychological crises.