Objective To examine differences in health-related quality of life (HRQOL) in stroke survivors with and without apathy. Design Cross-sectional study. Setting Acute stroke unit in a regional hospital. Participants Stroke survivors (N=391) recruited from the acute stroke unit. Interventions Not applicable. Main Outcome Measures Participants were divided into apathy and nonapathy groups. Participants who scored >36 on the Apathy Evaluation Scale, clinician's version formed the apathy group. HRQOL was measured with the 2 component scores, mental component summary (MCS) and physical component summary (PCS), of the Medical Outcomes Study 12-Item Short-Form Health Survey (SF-12). Demographic and clinical information were obtained with the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), Mini-Mental State Examination (MMSE), and Geriatric Depression Scale (GDS). Results Thirty-six (9%) participants had apathy. The apathy group had significantly lower MCS and PCS scores. After adjusting for sex, education, diabetes mellitus, and NIHSS, MMSE, GDS, and BI scores, the MCS score in the apathy group remained significantly lower. Conclusions Apathy has a significant negative effect on HRQOL in stroke survivors, particularly on their mental health. Interventions for apathy could improve the HRQOL of stroke survivors. © 2014 by the American Congress of Rehabilitation Medicine.