Non-suicidal self-injury (NSSI) in childhood is not well documented, especially among youth with pediatric bipolar disorder (PBD). The current study evaluated prevalence and correlates of NSSI, and its impact on intervention response, in a randomized trial of Child- and Family-Focused Cognitive-Behavioral Therapy (CFF-CBT) versus Treatment As Usual (TAU), adjunctive to pharmacotherapy. This study included 72 children ages 7–13 (58% male) with PBD. NSSI and correlates were assessed at baseline; mood and psychiatric severity were measured longitudinally. NSSI was common: 31% endorsed NSSI behaviors; 10% reported thoughts of NSSI, in the absence of behaviors. Children engaging in NSSI reported higher depression, psychosis, suicidality, and hopelessness; lower self-esteem; and reduced family help-seeking in univariate analyses. In a multivariate logistic regression, high child depression and psychosis, and low family help-seeking, remained significantly associated with baseline NSSI. In mixed-effects regression models, presence of NSSI at baseline did not influence the response of depressive symptoms to treatment. Children who endorsed NSSI experienced steeper response trajectories for psychiatric severity, regardless of treatment group. Youth who denied NSSI showed poorer response to TAU for manic symptoms; mania trajectories in CFF-CBT were similar across youth. Thus, NSSI in PBD is common and associated with impairment. As children might engage in NSSI for different reasons, the function of NSSI should be considered in treatment. Since children without NSSI fared worse in TAU, it may be important to ensure that youth with PBD receive structured, intensive interventions. CFF-CBT was efficacious regardless of NSSI, and thus shows promise for high-risk children with PBD.