The COVID-19 pandemic has significantly impacted the mental health of human beings since 2020, especially the young people and the pre-existing marginalized groups such as men who have sex with men (MSM). During the COVID-19 pandemic, the multi-country outbreak of mpox in 2022 additionally posed a significant stress on the most-affected communities (i.e., MSM). This study investigated the level of depressive symptoms and its multifaceted associated factors among Chinese young men who have sex with men (YMSM) in this unique period. In September 2022, a large-scale cross-sectional survey was conducted among YMSM aged 18–29 years across six representative provinces in China. Hierarchical regression analysis was performed to test the various types of associated factors of depressive symptoms. Among the 2493 participants, 65.6 % (n = 1638) reported mild to severe depressive symptoms. The hierarchical regression analysis identified that depressive symptoms was significantly positively associated with unemployment, having substance use in the past 6 months, a higher level of MSM self-stigma, incompletion of COVID-19 vaccination, greater mpox risk perception, and presence of mpox related-like symptoms. This study used the facility-based sampling method to recruit the participants, which may lead to selection bias. Chinese YMSM faced significant mental health challenges during the concurrent epidemics of COVID-19 and mpox, which was associated with their socio-economic status, risk behaviors, stigma, and multiple diseases-related variables. Proactive measures may hold promise as effective strategies for mitigating mental distress among marginalized groups during public health crises. •YMSM experienced severe depressive symptoms in dual-threat context in China.•Identifies key influencing factors across demographic and psychosocial realms.•Urges tailored mental health support for YMSM during health emergencies.•Recommends proactive mental health measures like campaigns and counseling.