Introduction: The knowledge of clinical spectrum and epidemiological profile of critically ill children plays a significant role in the planning of health policies that would mitigate various factors related to the evolution of diseases prevalent in these sectors. The data collected enable prospective comparisons to be made with benchmark standards including regional and international units for the continuous pursuit of providing essential health care and improving the quality of patient care. Purpose: To study the clinical spectrum and epidemiological profile of the critically ill children admitted to the pediatric intensive care unit at a tertiary care center in South India. Materials and Methods: Descriptive data were collected retrospectively from the Hospital medical records between 2013 and 2016. Results: A total of 1833 patients were analyzed during the 3-year period, of which 1166 (63.6%) were males and 667 (36.4%) were females. A mean duration of stay in pediatric intensive care unit (PICU) was 2.21 +/- 1.90 days. Respiratory system was the most common system affected in our study 738 (40.2 %). Acute poisoning in children constituted 99 patients (5.4%). We observed a mortality rate of 1.96%, with no association with age or sex. The mortality rate was highest in infants below 1-year of age (50%). In our study, the leading systemic cause for both admission and death was the respiratory system. Conclusion: This study analyses the epidemiological pattern of patients admitted to PICU in South India. We would also like to emphasize on public health prevention strategies and community health education which needs to be reinforced, especially in remote places and in rural India. This, in turn, would help in decreasing the cases of unknown bites, scorpion sting, poisoning and arthropod-borne illnesses, which are more prevalent in this part of the country.