Having same-sex partners is linked to poor psychological health and increased risk of suicide attempt. This link seems to be stronger for men than women. However, in France, there have been few studies of population samples, and the size of these studies does not always allow an in-depth analysis of these associations. This study explored these associations by analysing data from a large epidemiological survey conducted in France from 2012 to 2019 that included 84,791 women and 75,530 men. The frequencies and risk ratios of depression, suicide attempts, alcohol dependence and regular cannabis use were calculated regarding two groups: those with only the other sex partners and those with any same sex partners. Risk of alcohol addiction and cannabis use was greatly increased for women who had homosexual relations, even after adjustment for social, demographic and sexual life factors, which was not the case for men. However, risk of depression and suicide attempts was increased for men who had homosexual relations; this was also true for women but to a lesser extent. The estimates remained unchanged after stratifying the population by three distinct social groups defined by education level. The analysis of these differences was possible because of the large sample size of the CONSTANCES survey and its recruitment in the general population. This study helps increase knowledge of the health of sexual minorities. It can help clinicians pay more attention to the potential distress of their patients and can continue to inform policymakers of the effects of discrimination and stigmatisation linked to homosexual behaviour. •Depression and suicide attempts are frequent among persons with same-sex partners.•Excess risk of depression associated with same-sex partners is higher for men than women.•Alcohol dependence and regular cannabis use are frequent for women with same-sex partners.•Excess risk of psychoactive drug use associated with same-sex partners is increased for women.•Globally, these excess risks are similar regardless of education level.