Background and purpose Post‐stroke aphasia is associated with a reduced quality of life (QoL) and higher risk of depression. Few studies have addressed the effect of coping with aphasia. Our aim is to evaluate the impact of post‐stroke aphasia on self‐reported QoL and symptoms of depression. Methods This was a cross‐sectional prospective case–control study. Cases involved patients with post‐stroke aphasia included in the DULCINEA trial (NCT04289493). Healthy controls were recruited using snowball sampling. All subjects completed the following questionnaires: General Health Questionnaire (GHQ‐12), Stroke Aphasia Quality of Life Scale (SAQOL‐39), Communicative Activity Log (CAL) and Stroke Aphasic Depression Questionnaire (SADQ‐10). Results Twenty‐three patients (eight women; mean age 62.9 years) and 73 controls (42 women; mean age 53.7 years) were included. Cases scored lower than controls in perception of health (GHQ‐12: median 3 IQR 1; 6 vs. 0 IQR 0; 2) and perception of QoL (SAQOL‐39: median 3.6 IQR 3.3; 40 vs. 4.6 IQR 4.2; 4.8). Functional communication (CAL: median 135 IQR 122; 148 vs. 94 IQR 74; 103) and SAQOL‐39 communication subscale (median 2.7 IQR 2.1; 3.2 vs. 4.8 IQR 4.6; 5.0) were also significantly lower in the case group. Notably, cases reported fewer depressive symptoms than controls (SADQ‐10: median 11 IQR 9; 15 vs. 13 IQR 11; 16; p = 0.016). A mediational analysis revealed that the relationship between post‐stroke aphasia and depression was not mediated by functional communication. Conclusions Although communication difficulties impact the QoL of patients with post‐stroke aphasia, such patients report fewer depressive symptoms on the SADQ‐10 scale than healthy people, with no differences in scores related to social participation.