Besides causing serious threats to people’s physical health and lives, pandemics can lead to psychological distress. This study aimed to investigate the relationship between the COVID-19 pandemic and mental health among adults in Croatia and its association with sociodemographic factors, perceptions of pandemic, locus of control, coping with stress and perceived social support. A cross-sectional, observational study was conducted using a snowball sampling technique. The online survey collected information on sociodemographics, chronic health conditions, self-isolation measure, perception of COVID-19, mental health status, locus of control, coping with stress and perception of social support. Mental health status was assessed by the Depression, Anxiety and Stress Scale (DASS-21). A total of 1482 participants (252 males and 1230 females) completed the study. The mean age of the participants was 33.3 ± 12.2 years, 43 % of the participants had elevated levels of anxiety and 18 % suffered from severe and extremely severe anxiety, 33 % had elevated levels of depression and 12 % suffered from severe and extremely severe depression, and 55 % had elevated levels of stress with 13 % suffering from severe and extremely severe stress. The strongest predictors of mental health symptoms were coping with stress, locus of control, and perceived social support. These results highlight the necessity of implementing psychological interventions during the pandemic to improve the mental health of the adults and vulnerable groups in particular that should include identified factors associated with better mental health status such as coping with stress focused on problem, social diversion and social support.