Obstructive sleep apnea (OSA) is associated with the progression of cardiovascular diseases, arrhythmias, and sudden cardiac death (SCD). However, the acute impacts of OSA and its consequences on heart function are not yet fully elucidated. We hypothesized that desaturation events acutely destabilize ventricular repolarization, and the presence of accompanying arousals magnifies this destabilization. Ventricular repolarization lability measures, comprising heart rate corrected QT (QTc), short-time-variability of QT (STVQT), and QT variability index (QTVI) were calculated before, during, and after 20955 desaturations from lead II electrocardiography signals of 492 suspected OSA patients (52% men). Variations in repolarization parameters were assessed during and after desaturations, both with and without accompanying arousals, and groupwise comparisons were performed based on desaturation duration and depth. Regression analyses were utilized to investigate the influence of confounding factors, comorbidities, and medications. The standard deviation (SD) of QT, mean QTc, SDQTc, and STVQT increased significantly ( p<0.01) while QTVI decreased ( p<0.01) during and after desaturations. The changes in SDQT, mean QTc, SDQTc, and QTVI were significantly amplified ( p<0.01) in the presence of accompanying arousals. Desaturation depth was an independent predictor of increased SDQTc (β=0.405, p<0.01), STVQT (β=0.151, p<0.01), and QTVI (β=0.009, p<0.01) during desaturation. Desaturations cause acute changes in ventricular repolarization, with deeper desaturations and accompanying arousals independently contributing to increased ventricular repolarization lability. This may partially explain the increased risk of arrhythmias and SCD in OSA patients, especially when the OSA phenotype includes high hypoxic load and fragmented sleep.