Background Aphasia severity is known to affect quality of life (QoL) in stroke patients, as is mood disorders, functional limitations, limitations on activities of daily life, economic status and level of education. However, communication limitation or fatigue has not been explored in this specific population. Objective We aimed to investigate whether these factors were associated with QoL in patients with aphasia after stroke. Methods Patients with aphasia were included from April 2014 to November 2017 after a first stroke and were followed for 2 years post-stroke. QoL was assessed at follow-up by the French Sickness Impact Profile 65 (SIP-65). We explored predictors such as mood disorders, communication impairment, fatigue, limitations on activities of daily life, and aphasia severity in addition to socio-demographic factors. Results We included 32 individuals (22 men; mean age 60.7 [SD 16.6] years) with aphasia after a first stroke. Poor QoL as assessed by the SIP-65 was significantly associated (Pearson correlations) with increased severity of aphasia initially (P = 0.008) and at follow-up (P = 0.01); increased communication activity limitations at follow-up (P < 0.001); increased limitations on activities of daily life at baseline (P = 0.008) and follow-up (P < 0.001); increased fatigue at follow-up (P = 0.001); and increased depression symptoms at follow-up (P = 0.001). On multivariable analysis, QoL was associated with communication activity limitations, limitations on activities of daily life, fatigue and depression, explaining more than 75% of the variance (linear regression R2 = 0.756, P < 0.001). The relative importance in predicting the variance was 32% for limitations on activities of daily life, 21% fatigue, 23% depression and 24% communication activity limitations. Conclusion Aphasia severity, mood disorders and functional limitations may have a negative effect on QoL in patients with aphasia. Also, for the first time, we show that fatigue has an important impact on QoL in this population. Specific management of this symptom might be beneficial and should be explored in future studies.< Réduire