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Spontaneous bile duct perforation in the newborn is rare, with less than 150 cases reported. A term male newborn presented with abdominal distention and respiratory distress on the first day of life. Paracentesis revealed 420 mL of bile without succus or meconium, and laparoscopic washout and drainage was performed. A follow-up contrast enema several days later revealed a microcolon. The second operation confirmed the spontaneous bile duct perforation, but also revealed meconium ileus with ileal perforation and thick meconium. A sweat chloride study was abnormal and the patient was homozygous for the delta-F508 mutation. This is the first reported case of spontaneous bile duct perforation in association with meconium ileus or cystic fibrosis.