BACKGROUND: In the Netherlands, more than half of the teachers working in primary education experience high levels of work stress. Compared to other professions, teachers are more likely to drop out from work and develop mental illnesses. Almost one in five even choose a new profession within 5 years after starting as a teacher. This indicates an urgent need for interventions to reduce stress levels in teachers. However, few evidence-based effective interventions targeting stress and work-related problems in the primary educational system are available. AIM: In the current paper, we describe the protocol for a randomized controlled study (RCT) comparing an 8-week mindfulness-based stress reduction (MBSR) intervention with a wait list control condition in primary school teachers. We hypothesize that teachers who participate in the MBSR programme will report less stress (primary outcome) than those in the control group at post-test and at 3-month follow-up. We also expect a decrease in teachers' absenteeism and improvements of mental health, teacher skills, classroom climate quality and the pupil-teacher relationship (secondary outcomes). Finally, we hypothesize that self-compassion, mindfulness skills and emotion regulation skills could mediate effects. METHODS/DESIGN: A mixed-method study will be conducted among N=155 Dutch primary school teachers (grade 1 to 6). The quantitative study will be an RCT, in which teachers will be randomly allocated to the MBSR or waiting list control condition. Trial participants will not be made actively aware of their condition. The data analysts will be blinded. Online questionnaires will be sent to teachers before and after the MBSR programme, and at 3-month follow-up. Information about absenteeism will be collected. In the qualitative part of the study, we will interview teachers to examine their perceived effects of MBSR on their teaching skills, the classroom climate quality and the pupil-teacher relationship. DISCUSSION: This protocol paper describes a mixed-method study design with an RCT and a qualitative evaluation to evaluate an MBSR programme on perceived stress among primary school teachers. If the MBSR programme proves to be effective, it could be implemented as a programme to reduce stress and improve mental health and teaching outcomes in primary school teachers. TRIAL REGISTRATION: Nederland Trial Register NL. Registered on 19 November 2019-retrospectively registered, https://www.trialregister.nl/trial/8171.