Introduction Obstructive sleep apnea (OSA) has been linked with erectile dysfunction (ED), but it is unknown whether this association is maintained in the presence of other risk factors for ED. Aim The aim of this study was to evaluate the relationship between ED/sexual dysfunction and polysomnographic measures of sleep apnea in patients with known risk factors for ED. Methods Prospective cross-sectional analysis of 401 male patients undergoing in-lab polysomnography for suspected OSA. Erectile (EF) and sexual function were assessed by the 15-item International Index of Erectile Function (IIEF-15) questionnaire. Main Outcome Measures Severity of OSA via apnea–hypopnea index (AHI) and mean/lowest nocturnal oxygen saturation (SaO2). The IIEF-15 including the sexual domains: EF, intercourse satisfaction, orgasmic function, sexual desire, and overall satisfaction. Results OSA (AHI > 5/h) was diagnosed in 92% of patients. ED (EF subdomain ≤ 25) was present in 69% of patients with, and 34% of patients without OSA (P < 0.001). Multivariate stepwise regression analyses including known risk factors for ED, such as age, obesity, coronary heart disease, peripheral occlusive disease, hypertension, diabetes, prostate surgery, and β-blocker treatment, and measures of sleep apnea identified mean nocturnal SaO2 as independently associated with ED (P = 0.002; mean [95% CI] normalized slope 0.126 [0.047; 0.205]). Age (P < 0.001), peripheral occlusive disease (P = 0.001), prostate surgery (P = 0.018), and hypertension (P = 0.021) were confirmed as risk factors for ED, but did not abolish the sleep apnea-associated risk. Similar results were obtained for sexual dysfunction. Logistic regression analysis using the diagnosis of ED (EF subdomain ≤ 25) as binary dependent variable confirmed that mean nocturnal SaO2 (P = 0.012), as well as age (P < 0.001) were independently associated with ED. Conclusions ED and overall sexual dysfunction were highly prevalent in patients with suspected OSA. Irrespective of known risk factors, mean nocturnal SaO2 was an additional, independent correlate of these dysfunctions, suggesting that OSA-related intermittent nocturnal hypoxemia specifically contributes to their development.