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Abstract Background According to the projections of the World Health Organization, 15% of all disabilities will be associated with mental illnesses by 2020. One of the mental disorders with the largest social impacts due to high personal and family costs is psychosis. Among the most effective psychological approaches to treat schizophrenia and other psychotic disorders at the world level is cognitive behavioral therapy. Recently, cognitive behavioral therapy has introduced several tools and strategies that promote psychological processes based on acceptance and mindfulness. A large number of studies support the effectiveness of mindfulness in dealing with various mental health problems, including psychosis. This study is aimed at determining the efficiency of a mindfulness-based program in increasing cognitive function and psychological well-being in patients with a first episode of schizophrenia and a high risk mental state (those at risk of developing an episode of psychosis). Methods and design This is an experimentally designed, multi-center randomized controlled trial, with a 3-month follow-up period. The study participants will be 48 patients diagnosed with schizophrenia (first episode) and 48 with a high-risk mental state, from Santiago, Chile, aged between 15 and 35 years. Participants will be submitted to a mindfulness-based intervention (MBI), which will involve taking part in eight mindfulness workshops adapted for people with psychosis. Workshops will last approximately 1.5 hours and take place once a week, over 8 weeks. The primary outcome will be the cognitive function through Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and the secondary outcome will be psychological well-being measured by self-reporting questionnaires. Discussion The outcomes of this trial will add empirical evidence to the benefits and feasibility of MBIs for the psychotherapeutic treatment of patients with schizophrenia and high-risk mental states in reducing cognitive impairment in attention, working memory, and social cognition, as well as increasing the psychological well-being by empowering the patients’ personal resources in the management of their own symptoms and psychotic experiences. Trial registration ISRCTN registration number ISRCTN24327446 . Registered on 12 September 2016.