Both obstructive sleep apnea (OSA) and decreased serum lipoprotein(a) (Lp(a)) concentrations are associated with insulin resistance. However, their interaction effect on insulin resistance has never been investigated. Therefore, we performed a cross-sectional study on OSA-suspected Chinese Han participants. Laboratory-based polysomnographic variables, biochemical indicators, anthropometric measurements, and medical history were collected. Linear regression and binary logistic regression analyses with interaction terms were used to investigate the potential effects of the interaction between the severity of OSA (assessed by the apnea-hypopnea index (AHI)) and Lp(a) concentrations on insulin resistance (assessed by the homeostasis model assessment of insulin resistance (HOMA-IR)), after adjusting for potential confounders including age, gender, body mass index, waist-to-hip circumference ratio, mean arterial pressure, smoking status, drinking status, and lipid profiles. A total of 4,152 participants were enrolled. In the OSA-suspected population, AHI positively correlated with insulin resistance and serum Lp(a) concentrations independently and inversely correlated with insulin resistance. In addition, the interaction analysis showed that the linear association between lgAHI and lgHOMA-IR was much steeper and more significant in subjects with relatively low Lp(a) concentrations, suggesting a significant positive interaction between lgLp(a) and lgAHI on lgHOMA-IR (P = 0.013). Furthermore, the interaction on a multiplicative scale also demonstrated a significant positive interaction (P = 0.044). A stronger association between AHI quartiles and the presence of insulin resistance (defined as HOMA-IR > 3) could be observed for participants within lower Lp(a) quartiles. In conclusion, a significant positive interaction was observed between OSA and decreased Lp(a) with respect to insulin resistance. This association might be relevant to the assessment of metabolic or cardiovascular disease risk in OSA patients.