Abstract Background Patients with obsessive-compulsive disorder (OCD) present difficulties in the cognitive regulation of emotions, possibly because of inefficient recruitment of distributed patterns of frontal cortex regions. The aim of the present study is to characterize the brain networks, and their dysfunctions, related to emotion regulation alterations observed during cognitive reappraisal in OCD. Methods Adult patients with OCD (n = 31) and healthy controls (HC; n = 30) were compared during performance of a functional magnetic resonance imaging cognitive reappraisal protocol. We used a free independent component analysis approach to analyze network-level alterations during emotional experience and regulation. Correlations with behavioral scores were also explored. Results Analyses were focused on six networks encompassing the frontal cortex. OCD patients showed decreased activation of the frontotemporal network in comparison with HC (F(1,58) = 7.81, p = 0.007) during cognitive reappraisal. A similar trend was observed in the left frontoparietal network. Conclusions The present study demonstrates that patients with OCD show decreased activation of specific networks implicating the frontal cortex during cognitive reappraisal. These outcomes should help to better characterize the psychological processes modulating fear, anxiety, and other core symptoms of patients with OCD, as well as the associated neurobiological alterations, from a system-level perspective.