Background While cognitive-behavioral therapy for insomnia constitutes the first-line treatment for chronic insomnia, only few reports have investigated how sleep architecture relates to response to this treatment. In this pilot study, we aimed at determining whether sleep spindle density at pre-treatment predicts treatment response to cognitive behavioral therapy for insomnia. Methods Twenty-four participants with chronic primary insomnia took part in a 6-week cognitive behavioral therapy for insomnia performed in groups of 4 to 6 participants. Treatment response was assessed using the Pittsburgh Sleep Quality Index and the Insomnia Severity Index measured at pre- and post-treatment and at 3- and 12-months follow-up assessments. Secondary outcome measures were extracted from sleep diaries over seven days and one overnight polysomnography, obtained at pre- and post-treatment. Spindle density during stages N2-N3 sleep was extracted from polysomnography at pre-treatment. Hierarchical linear modeling analysis assessed whether sleep spindle density predicted response to cognitive behavioral therapy. Results After adjusting for age, sex and education level, lower spindle density at pre-treatment predicted poorer response over the 12-months follow-up, as reflected by smaller reduction in Pittsburgh Sleep Quality Index over time. Reduced spindle density also predicted lower improvements in sleep diary sleep efficiency and wake after sleep onset immediately after treatment. There were no significant associations between spindle density and changes in the Insomnia Severity Index or polysomnography variables over time. Conclusion These preliminary results suggest that inter-individual differences in sleep spindle density in insomnia may represent an endogenous biomarker predicting responsiveness to cognitive behavioral therapy. Insomnia with altered spindle activity might constitute an insomnia subtype characterized by a neurophysiological vulnerability to sleep disruption associated with impaired responsiveness to cognitive behavioral therapy.