ABSTRACT: Abstract Background Cognitive remediation (CR) is an evidence-based behavioral intervention for cognitive impairment in schizophrenia. Although the effectiveness of CR is well stablished, its effects are modest, especially in terms of functional outcome. There is an emerging literature suggesting that adding aerobic exercise to CR may exert synergistic effects. Despite these promising reports, the extent to which aerobic exercise in combination with CRT can improve cognitive and daily functioning in multiepisode schizophrenia and schizoaffective disorder remains unclear. Methods This is a single-blinded, randomized clinical trial (NCT02864576) with two different groups: 1) patients with multiepisode schizophrenia or schizoaffective disorder receiving 3-month Aerobic exercise plus CR treatment (three weekly sessions, 40min of Aerobic exercise and 90min of CR), and 2) patients with multiepisode schizophrenia or schizoaffective disorder receiving Healthy lifestyle promotion plus CR treatment (three weekly sessions, 40min of Healthy lifestyle promotion and 90min of CR). Primary outcome measures were the MATRICS Consensus Cognitive Battery (MCCB) and the Global Assessment of Functioning (GAF), which were assessed (among others) at baseline and immediately after treatment. For the present work, the sample included in the analysis were 34 patients for whom cognitive data were available. Treatment effects on neurocognition and functional outcome were analyzed by applying the multivariate general linear model (GLM) repeated measures. Results After treatment, both groups exhibited a significant improvement in MCCB visual learning memory (F=14.298, p= 0.001), working memory (F=6.626, p= 0.015) and speed of processing (F=16.344, p= 0.001) domains. However, no significant benefits were evidenced for problem solving (F=2.143, p= 0.153), verbal learning memory (F= 0.321, p= 0.575) and attention/vigilance (F=0.740, p= 0.397) domains. Functional outcome, as measured by the GAF, was more improved in the Aerobic exercise plus CR group than in the Healthy lifestyle promotion plus CR group (F=4.248, p= 0.047). Discussion Our preliminary findings indicate that combining aerobic exercise with cognitive remediation may promote a large impact on functional outcome in patients with multiepisode schizophrenia or schizoaffective disorder.