This study examined the prevalence of mental distress among groups in Afghanistan considered to be at risk. Data were drawn from a representative cross-sectional disability survey carried out in Afghanistan including 5,130 households in 171 clusters throughout the 34 provinces of the country. The sample included 838 nondisabled control participants aged above 14, and 675 disabled participants. Results showed that various vulnerable groups (disabled people, the unemployed, the elderly, minority ethnic groups, as well as widowed, divorced or separated women) were at higher risk of experiencing mild to severe mental health problems. The adjusted odds ratio for war-related disability compared to nondisabled was 4.09 (95% confidence interval 2.09 to 7.99) for mild mental distress disorders, and 7.10 (3.45-14.5) and 14.14 (3.38-59.00) for moderate or severe mental distress disorders, respectively. Women with disabilities (whatever the cause of impairment) when compared with nondisabled men, as well as poorer segments of society compared to the richest, had a higher prevalence of mental health problems. Women with non-war-related disabilities compared with nondisabled men were respectively 3.35 (1.27-8.81) and 8.57 (3.03-24.1) times more likely to experience mild or moderate mental distress disorders. People who experience multiple vulnerabilities are more at risk of deteriorating mental health in conflict zones. The study shows that mental health, in times of war, is influenced by a combination of demographic and socioeconomic characteristics linked to social exclusion mechanisms that were in place before the conflict began and that are redefined in relation to the changing social, cultural, and economic contexts. Mental health policies and programmes must prioritise the most vulnerable segments of Afghan society.