Despite evidence for the efficacy of interpersonal psychotherapy (IPT) for depression, there remains little understanding of its specific change-promoting ingredients. This study aimed to establish candidate change mechanisms by identifying whether patients’ interpersonal (theory-specific) and cognitive (theory-nonspecific) characteristics change in an adaptive direction during IPT, and whether such changes differentially relate to depression reduction and improvement in global functioning. The four interpersonal variables and one cognitive variable measured all changed significantly in an adaptive direction, with medium to large effect sizes. Reduced interpersonal problems were marginally associated with self-reported depression reduction (β = 2.846, p = .062), and greater satisfaction with social support was marginally associated with depression reduction (β = -1.423, p = .081). Unexpectedly, reduced romantic relationship adjustment was related to depression reduction (β = 2.028, p = .008 for self-rated depression and β = 1.474, p = .022 for clinician-rated depression), and increased attachment avoidance was marginally related to better clinician-rated global functioning (β = 1.501, p = .09). Thus, theory-relevant interpersonal variables emerged as candidate change mechanisms, and the findings are discussed with respect to their research and practice implications.