Activation of spinal microglia following peripheral nerve injury is a central component of neuropathic pain pathology. While the contributions of microglia-mediated immune and neurotrophic signalling have been well-characterized, the phagocytic and synaptic pruning roles of microglia in neuropathic pain remain unknown. Here, we show that peripheral nerve injury induces engulfment of dorsal horn synapses by microglia, leading to a preferential loss of inhibitory synapses. This synapse removal is dependent on the microglial complement-mediated synapse pruning pathway, as mice deficient in complement C3 do not exhibit synapse elimination. Furthermore, pharmacological inhibition of the complement protein C1q prevents dorsal horn inhibitory synapse loss and attenuates neuropathic pain. Thus, these results demonstrate that the complement pathway promotes persistent pain hypersensitivity via microglia-mediated engulfment and loss of inhibitory synapses in the dorsal horn of the spinal cord, revealing C1q as a novel therapeutic target in neuropathic pain.