Unlike best practice guidelines for detecting and addressing medication side effects, there are no widely adopted guidelines to help therapists identify and address the possible negative effects of psychotherapy. Psychotherapy is a first-line evidence-based intervention for youth depression and anxiety, but the literature contains few studies of psychotherapy’s potential negative effects, and even fewer direct youth reports of their negative psychotherapy experiences. A mixed-methods study design was used to study youth with self-reported depression and/or anxiety and measure negative experiences associated with psychotherapy treatment. Youth were recruited from a larger study. Qualitative and quantitative data were collected from 45 youth with psychotherapy experience. Study design was informed by feedback from youth with lived experience of mental health challenges. Youth completed standardized measures of psychopathology, treatment effects, and detailed qualitative interviews. All youth experienced at least one negative effect during psychotherapy, and 30 youth (66.7%) attributed a negative effect as ‘caused’ by psychotherapy. While this attribution did not significantly differ based on severity of underlying current psychopathology, effect size estimates suggest moderate to large group differences regarding internalizing issues and baseline coping skills. Four major qualitative themes were identified from the interviews, summarizing the negative experiences of psychotherapy: (1) Barriers Experienced in Psychotherapy; (2) Concerns about Therapist; (3) Concerns about Therapy Itself; (4) Negative Experiences as a part of the Therapeutic Process. No youth raised any of these concerns directly with their therapists. These data support the need for validated, systematic assessment of psychotherapy’s negative effects among youth, with the aim of improving engagement and treatment outcomes.