Mothers' knowledge and management of pain in infants were assessed in this study. A total of 130 mothers from two health centres in Ile Ife, Southwest, Nigeria were selected by systematic sampling method. Only 3.8% indicated that neonates experience pain. Malaria (46.2%) was the major cause of pain identified. Analgesic/antimalarials (56.9%) and breastfeeding (16.9%) are used in pain relief. To improve the quality of life of infants, mothers must be educated on the assessment, early detection and management of pain.