Reduced pain perception while being distracted from pain is an everyday example of how cognitive processes can interfere with pain perception. Previous neuroimaging studies showed distraction-related modulations of pain-driven activations in various cortical and subcortical brain regions, but the precise neuronal mechanism underlying this phenomenon is unclear. Using high-resolution functional magnetic resonance imaging of the human cervical spinal cord in combination with thermal pain stimulation and a well-established working memory task, we demonstrate that this phenomenon relies on an inhibition of incoming pain signals in the spinal cord. Neuronal responses to painful stimulation in the dorsal horn of the corresponding spinal segment were significantly reduced under high working memory load compared to low working memory load. At the individual level, reductions of neuronal responses in the spinal cord predicted behavioral pain reductions. In a subsequent behavioral experiment, using the opioid antagonist naloxone in a double-blind crossover design with the same paradigm, we demonstrate a substantial contribution of endogenous opioids to this mechanism. Taken together, our results show that the reduced pain experience during mental distraction is related to a spinal process and involves opioid neurotransmission.