||OBJECTIVE: To explore the hypothesis that insomnia may increase the risk of coronary heart disease through inflammatory mechanisms. METHODS: The association of high-sensitivity C-reactive protein (hsCRP) with self-reported symptoms of insomnia was examined. Participants were 8547 men and nonpregnant women who answered one or more insomnia-related questions and who had available hsCRP measurements in the Nord-Trondelag Health Study. In multivariable linear regression analyses of the logarithm of hsCRP, we adjusted for established cardiovascular risk factors, psychosocial distress, chronic pain, and chronic somatic disorders. RESULTS: Among men, difficulties initiating sleep and nonrestorative sleep were associated with increasing hsCRP levels after adjusting for age (B = 0.07, 95% confidence interval [CI] = 0.01-0.14, p for trend = .02 and B = 0.09, 95% CI = 0.02-0.15, p for trend = .006), but after multivariable adjustment, the associations were attenuated (B = 0.03, 95% CI = -0.03 to 0.09, p for trend = .30 and B = 0.06, 95% CI = -0.00 to 0.12, p for trend = .05). HsCRP was not associated with other insomnia-related symptoms. In women, there was no evidence for any association of symptoms of insomnia with hsCRP levels. Results indicated sex differences in the association between sleep characteristics and CRP (difficulties maintaining sleep, p interaction = .018; cumulative number of symptoms of insomnia, p interaction = .014; and symptoms of insomnia influencing work performance, p interaction = .039). CONCLUSIONS: There were no consistent associations between symptoms of insomnia and hsCRP levels. Our results do not support the hypothesis that inflammation, as reflected by elevated levels of hsCRP, is an important factor linking insomnia to coronary heart disease.