Background: Insomnia is common among patients with stable heart failure (HF) and associated with inflammation and altered autonomic function. Purpose: The purposes of this study were to examine the effects of cognitive behavioral therapy for insomnia (CBT-I) on the Hypothalamic Pituitary (HPA) Axis, autonomic function, inflammation and circadian rhythmicity and the associations between these biomarkers and insomnia, sleep characteristics, symptoms, functional performance, and sleep-related cognitions. Methods: We conducted a sub-analysis of a pilot randomized controlled trial (RCT) (NCT02827799) whose primary aim was to test the effects of CBT-I on insomnia. We randomized 51 patients with stable Class II-IV HF to CBT-I (n = 30) or attention control (n = 21). Participants completed wrist actigraphy and self-reported insomnia severity, sleep characteristics, sleep-related cognitions, daytime symptoms, and functional performance. We measured day and nighttime urinary free cortisol, melatonin sulfate, epinephrine and norepinephrine at baseline and 2 weeks after CBT-I and computed general linear models and partial correlations. Results: CBT-I had no effects on the biomarkers, but there were statistically significant negative cross-sectional correlations between the ratio of day/night urinary free cortisol and sleep