Objectives: Khuzdar, the largest city of Southern Balochistan, is endemic for malaria with API of 6. The study was aimed at comparing the clinico-lab profile of severe and uncomplicated malaria in the region and to determine any association with age. No such study is reported in the region so far. Methods: A prospective clinical observational study was conducted in Combined Military Hospital, Khuzdar between 2018 and 2020. A total of 210 Malaria patients, irrespective of age and gender were included. Cases were categorized into severe and uncomplicated according to WHO criteria. The clinical parameters and lab profile of severe and uncomplicated cases were compared and data was analyzed using SPSS 23.0. Categorical variables were analyzed for association of clinical features with severe malaria using Fisher exact test. Continuous variables were compared between uncomplicated and severe malaria using Mann-Whitney U –test. Statistical significance of lab parameters with type of malaria was derived using Kruskal Wallis. Results: Uncomplicated and severe cases were 191 (91%) and 19 (9%) respectively. Severe malaria was significantly associated with jaundice, bleeding from gums, epistaxis, pallor, vomiting, respiratory distress, thrombocytopenia, low Hb, raised serum bilirubin and raised PT (p value<0.05). In children, frequency of multiple complications was significantly higher than adult patients. (75% vs 25%, p-value 0.002).Overall case fatality of severe malaria was 5.2% (1/19). However, case fatality rate was 100% in cerebral malaria. Conclusions: Certain clinical and lab parameters can be used to predict prognosis and thus avoid adverse outcome in malaria patients. doi: https://doi.org/10.12669/pjms.37.7.4210 How to cite this:Khan M, Nisar H, Mushahid N. Clinical and Lab profile of severe and uncomplicated malaria: A prospective study from Khuzdar Balochistan. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.4210 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.