Background: (FM). Fibromyalgia (FM) is a very prevalent and debilitating chronic pain disorder that is difficult to treat. Mindfulness-based techniques are regarded as a very promising approach for the treatment of chronic pain and in particular FM. The Mindfulness-Oriented Recovery Enhancement (MORE) intervention, a mindfulness-based group intervention, has shown beneficial effects in opioid-treated chronic pain patients, including reduced pain severity, functional interference, and opioid dosing, by restoring neurophysiological and behavioral responses to reward. First evidence for a hypodopaminergic state and impaired reward processing in FM have been reported. However, little is known about its impact on dopamine (DA) function and in particular with regard to DA responses to monetary reward in FM. The aim of the present study protocol is to evaluate if MORE is able to restore the DA function in FM patients, in particular with regard to the DA responses to reward, and to reduce pain and mood complaints in FM.Methods/design: The present study is a multi-center RCT with 3 time points: before the intervention, after completion of the intervention and 3-months after completion of the intervention. Eighty FM patients will be randomly assigned to either the MORE intervention (N=40) or to a wait-list control group (N=40). Additionally a comparison group of healthy women (N=20) will be enrolled. The MORE intervention consists of eight 2-hour long group sessions administered weekly over a period of 8 weeks. Before and after the intervention, FM participants will undergo [18F] DOPA Positron Emission Tomography (PET) and functional MR imaging while performing a monetary reward task. The primary outcome will be endogeneous DA changes measured with [18F] DOPA PET at baseline, after the intervention (after 8 weeks for control group), and at 3 months’ follow-up. Secondary outcomes will be (1) clinical pain measures and FM symptoms using standardized clinical scales 2) functional brain changes 3) measures of negative and positive affect, stress and reward experience in daily life using the Experience Sampling method (ESM) 4) biological measures of stress including cortisol and alpha-amylase.Design: If the findings of this study confirm the effectiveness of MORE in restoring DA function, reducing pain and improving mood symptoms, MORE can be judged to be a promising means to improve quality of life in FM patients. The findings of this trial may inform health care providers about the potential use of the MORE intervention as a possible non-pharmacological intervention for FM.Trial registration: ClinicalTrials.gov NCT 04451564. Registered on 3 July 2020. The trial was prospectively registered.