Background: Post-stroke fatigue (PSF) is a common and often disabling symptom, the etiology of which is poorly understood. Sleep-disordered breathing (SDB) is also highly prevalent among stroke survivors. We explored the relationship between SDB and PSF over time in a bi-ethnic cohort. Methods: Ischemic stroke (IS) patients within the Brain Attack Surveillance in Corpus Christi (BASIC) project were identified through active and passive surveillance, and were offered home SDB screening with a well-validated cardiopulmonary sleep apnea testing device, the ApneaLink Plus. The primary exposure was the respiratory event index (REI). The primary outcome was PSF as measured by the SF-36 vitality scale (lower scores reflect greater fatigue). SDB and PSF were measured at baseline, 3, 6, and 12 months post-stroke. A linear regression model, using GEE to account for repeated measures, was used to examine the associations between REI and PSF at each time point adjusting for sociodemographics, stroke severity, depressive symptoms, pre-stroke fatigue, and comorbidities. Results: SDB screening and at least one PSF assessment were completed by 462 IS patients, who were 44% female, 61% Mexican American (MA), 26% non-Hispanic white, 7% Black, and 5% other race/ethnicity. Median NIHSS was 2 (IQR: 1-4). Multivariable regression model results are presented in the Table. Higher REI at 3 months was associated with greater PSF at 3 months (β= -1.87, 95%CI -3.47, -0.27), but there was no association between REI and PSF at 6 or 12 months. Across timepoints, female sex, depressive symptoms at time of assessment, pre-stroke medication for depression, higher levels of pre-stroke fatigue, and vascular risk factor burden were associated with greater PSF, whereas MA ethnicity was associated with less PSF. Conclusions: Higher REI was associated with greater PSF in the early post-stroke period, but no association was observed at 6 months and beyond. MA ethnicity seems to be protective against PSF.