Introduction: Admission to a pediatric intensive care unit (PICU) with a Staphylococcus aureus (SA) infection is associated with considerable mortality and morbidity. There is paucity of data about epidemiology of SA infection in a PICU. This study was aimed at elucidating the clinicoepidemiological profile and outcome of children admitted to ICU with S. aureus infection. Methods: This study was carried out in a PICU at a tertiary care hospital in northern India. Children admitted with culture positive S. aureus infection were enrolled in this study. Children suspected of having S. aureus infection on clinical grounds only without a positive culture were excluded from the study. Baseline characteristics of the subjects were recorded on admission and daily follow up maintained till death or discharge from PICU. The course during PICU stay, ensuing complication, and outcome was recorded. Results: There were 2,480 total admissions to the PICU during study period of one year, out of which 120 (4.83%) admissions had a culture proven S. aureus infection. Fifty-six (46.6%) were male and 64 (53.3%) were female. Most of the subjects fell in the age groups of 1–5 years and 10–15 years having 56 (46.6%) and 40 (33.3%) subjects, respectively. Pneumonia (43.3%), septicaemia (20.8), and bone/joint space infections (15%) were the three main clinical manifestations. Forty-two (35%) of specimens were reported as methicillin resistant. Incidence of methicillin resistant SA (MRSA) infection was 1.6 and that of methicillin sensitive SA (MSSA) 3.1 per 100 admissions to PICU. On sensitivity testing, none of the specimens was found to be vancomycin resistant. There were 240 total deaths in PICU during study period out of which 25 (10.4%) were observed from the study group. Mortality rate was 20.8%. Mortality was high in the MRSA group. Conclusion: The incidence of S. aureus infection and associated mortality is high in PICU. MRSA infection was more common in children admitted with chronic disease and is associated with higher mortality. Our study found a bimodal age distribution for serious staph infection, a finding that needs further evaluation.