Background This study investigated the prevalence of neuropathic pain (NP) among people affected by leprosy and its effects on functional limitation and health-related quality of life (HRQoL) in an endemic area in Northeast Brazil. Methods This is a cross-sectional study of 122 leprosy patients. Functional limitation and HRQoL were assessed using the Screening of Activity Limitation and Safety Awareness (SALSA) and WHO Quality-of-Life (WHOQoL-BREF) scales, respectively. Participants were assessed for the presence of pain and completed the Douleur Neuropathique 4 and the Brief Pain Inventory scales. Results The prevalence of NP was 59%. Participants with NP had higher SALSA scores than those without pain (median; IQR: 42; 32–49.5 vs 27.5; 24–34; p=0.002). Increasing SALSA scores were related to decreasing WHOQoL-BREF scores in the physical (r=−0.54; p<0.001), psychological (r=−0.33; p=0.002) and environmental (r=−0.22; p=0.01) domains, but not in the social domain (r=−0.14; p=0.10). Individuals with NP had the lowest scores in all domains compared with individuals without pain. Conclusions Appropriate tools and training of clinicians for diagnosing NP in leprosy patients are necessary for their appropriate management and better HRQoL outcomes.