Objectives. The purpose of this study is to investigate the relationship between plasma endocannabinoids and insulin resistance (IR) in patients with obstructive sleep apnea (OSA). Methods. A population of 64 with OSA and 24 control subjects was recruited. Body mass index (BMI), waist circumference, lipids, blood glucose and insulin, homeostasis model of assessment for insulin resistance index (HOMA-IR), anandamide (AEA), 1/2-arachidonoylglycerol (1/2-AG), and apnea-hypopnea index (AHI) were analyzed. Results. Fasting blood insulin (22.9 ± 7.8 mIU/L versus 18.5 ± 7.2 mIU/L, P < 0.05), HOMA-IR (2.9 ± 1.0 versus 2.4 ± 0.9, P < 0.01), AEA (3.2 ± 0.7 nmol/L versus 2.5 ± 0.6 nmol/L, P < 0.01), and 1/2-AG (40.8 ± 5.7 nmol/L versus 34.3 ± 7.7 nmol/L, P < 0.01) were higher in OSA group than those in control group. In OSA group, AEA, 1/2-AG, and HOMA-IR increase with the OSA severity. The correlation analysis showed significant positive correlation between HOMA-IR and AHI (r = 0.44, P < 0.01), AEA and AHI (r = 0.52, P < 0.01), AEA and HOMA-IR (r = 0.62, P < 0.01), and 1/2-AG and HOMA-IR (r = 0.33, P < 0.01). Further analysis showed that only AEA was significantly correlated with AHI and HOMA-IR after adjusting for confounding factors. Conclusions. The present study indicated that plasma endocannabinoids levels, especially AEA, were associated with IR and AHI in patients with OSA.