Abstract Objectives Further mechanistic insight on mind–body techniques for fibromyalgia (FMS) is needed. Arterial spin labelling (ASL) imaging can capture changes in regional cerebral blood flow (rCBF) that relate to spontaneous pain. Methods We recruited FMS patients undergoing either mindfulness-based stress reduction training (MBSR, n = 14) or a psychoeducational programme (FibroQoL, n = 18), and a control FMS group with no add-on treatment (n = 14). We acquired whole-brain rCBF maps and self-report measures at baseline and following treatment and explored interaction effects in brain perfusion between the treatment group and session with a focus on the amygdala, the insula and the anterior cingulate cortex (ACC). Results We identified a significant interaction effect in the amygdala, which corresponded with rCBF decreases following FibroQoL specifically. At baseline, rCBF in the amygdala for the FibroQoL group correlated with pain catastrophizing and anxiety scores, but not after treatment, suggesting a decoupling between activity in the amygdala and negative emotional symptoms of FMS as a consequence of treatment. Baseline rCBF correlated positively with pain symptoms in the ACC and the anterior insula across all patients; moreover, the correlation between rCBF changes post intervention in the insula and pain improvement was negative for both treatments and significantly different from the control group. We suggest that there is disruption of the typical relationship between clinical pain and activity as a product of these two nonpharmacological therapies. Conclusions We have demonstrated that different mind-to-body treatments correspond to differential changes in clinical symptoms and brain activity patterns, which encourages future research investigating predictors of treatment response. Trial Registration NCT02561416.