Out-of-hospital cardiac arrest (OHCA) is a leading cause of death worldwide, with cardiovascular disease (CVD) being a key risk factor. This study aims to investigate disparities in patient/OHCA characteristics and survival after OHCA among patients with versus without depression. This is a retrospective cohort study using data from the AmsteRdam REsuscitation Studies (ARREST) registry from 2008-2018. History of comorbidities, including depression, was obtained from the patient's general practitioner. OHCA survival was defined as survival at 30 days post-OHCA or hospital discharge. Logistic regression models were used to obtain crude and adjusted odds ratios (ORs) for the association between depression and OHCA survival and possible effect modification by age, sex, and comorbidities. The potential mediating effects of initial heart rhythm and provision of bystander cardiopulmonary resuscitation were explored. Among 5,594 OHCA cases, 582 individuals had pre-existing depression. Patients with depression had less favourable patient and OHCA characteristics and lower odds of survival after adjustment for age, sex, and comorbidities (OR 0.65, 95% CI 0.51-0.82), with similar findings by sex and age groups. The association remained significant among the Utstein comparator group (OR 0.63, 95% CI 0.45-0.89) and patients with return of spontaneous circulation (OR 0.60, 95% CI 0.42-0.85). Initial rhythm and bystander cardiopulmonary resuscitation partially mediated the observed association (by 27% and 7%, respectively). OHCA patients with depression presented more frequently with unfavourable patient and OHCA characteristics and had reduced chances of survival. Further investigation into potential pathways is warranted.