Hypoxic load is one of the main characteristics of obstructive sleep apnea (OSA) contributing to sympathetic overdrive and weakened cardiorespiratory coupling (CRC). Whether this association changes with increasing hypoxic load has remained obscure. Therefore, we aimed to study our hypothesis that increasing hypoxic load acutely decreases the CRC. We retrospectively analyzed the electrocardiography and nasal pressure signals in 5-min segment pairs (n = 36 926) recorded during clinical polysomnographies of 603 patients with suspected OSA. The segment pairs were pooled into five groups based on the hypoxic load severity described with the the total integrated area under the blood oxygen saturation curve during desaturations. In these severity groups, we determined the frequency-domain heart rate variability (HRV) parameters, the HRV and respiratory high-frequency (HF, 0.15-0.4 Hz) peaks, and the difference between those peaks. We also computed the spectral HF coherence between HRV and respiration in the HF band. The ratio of low-frequency (LF, 0.04-0.15 Hz) to HF power increased from 1.047 to 1.805 (p < 0.001); the difference between the HRV and respiratory HF peaks increased from 0.001 Hz to 0.039 Hz (p < 0.001); and the spectral coherence between HRV and respiration in the HF band decreased from 0.813 to 0.689 (p < 0.001) as the hypoxic load increased. The vagal modulation decreases and CRC weakens significantly with increasing hypoxic load. Thus, the hypoxic load could be utilized more thoroughly in contemporary OSA diagnostics to better assess the severity of OSA-related cardiac stress.