HIV disclosure to spouses can promote HIV prevention and facilitate support from those spouses; it can also cause mental health challenges for the spouses. We conducted a qualitative study of the mental health status and potential contributing factors of mental health challenges of spouses of men living with HIV in Sichuan, China. We interviewed 31 spouses whose husbands were living with HIV. Qualitative data were analyzed using content and thematic analyses. We found that mental health challenges were common among the spouses; leading challenges were themed as hopelessness, depression, and anxiety. Greater HIV knowledge, close relationship with husband, and psychological support may protect spouses from mental health challenges, whereas HIV-related stigma, heavy caregiving burden, and an unsupportive environment might be detrimental to mental health. Spouses of men living with HIV need mental health services, which should take into account a wide spectrum of contributors at individual, couple, and social levels.