Background:Harlequin ichthyosis is a rare and fatal fetal disorder, most often complicated by infection. Sepsis due to Vibrio cholerae is rare, especially in neonatology. The association between ichthyosis and Vibrio cholerae infection has never been described in medical literature. Introduction:We report the case of a newborn admitted to the neonatal intensive care unit, with a typical characteristics of Harlequin ichthyosis and a sepsis due to Vibrio cholerae, diagnosed with the blood culture. The outcome was fatal; characterized by death six hours after his hospitalization. Conclusion:Cases of Harlequin ichthyosis complicated with septicemia with Pseudomonas Aeruginosa have been described. Vibrio cholerae infections are usually confined to the gastrointestinal tract but some species, especially non-01 strains, can cause extra-intestinal infections including septicemia and meningitis.