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Mindfulness-based practice is a form of cognitive/affective training that may help reduce suffering by attenuating maladaptive anticipatory processes. This study's objective was to examine the pain modulating impact of classical fear learning in meditation practitioners.The hyperalgesic effects of pain expectation and uncertainty were assessed outside formal meditation in 11 experienced meditators (>1000 hours) compared with meditation-naive controls during a Pavlovian classical fear-conditioning paradigm involving two visual stimuli (CS+/CS−), one of which (CS+) co-terminated with a noxious electrical stimulus (unconditioned stimulus) on 50% of trials. A Rescorla-Wagner/Pearce-Hall hybrid model was fitted onto the conditioned skin conductance responses using computational modeling to estimate two learning parameters: expected shock probability and associability (i.e., uncertainty).Using a scale ranging between 0 (no pain) and 100 (extremely painful), meditators reported less pain (M = 19.9, SE = 5.1 for meditators, M = 32.4, SE = 2.4 for controls) but had comparable spinal motor responses (nociceptive flexion reflex) to the unconditioned stimulus. Multilevel mediation analyses revealed that meditators also exhibited reduced hyperalgesic effects of fear learning on higher-order pain responses but comparable effects on the nociceptive flexion reflex. These results suggest that mindfulness affects higher-order perceptual processes to a greater extent than from descending inhibitory controls. Furthermore, meditators showed reduced hyperalgesic effects of fear conditioning with no significant group difference in conditioned learning as evidenced by discriminative anticipatory skin conductance responses and learning parameters derived from computational modeling.These results highlight potential mechanisms underlying mindfulness-related hypoalgesia, relevant to clinical conditions in which repeated pain exposure might reinforce hyperalgesic processes through fear conditioning.