Introduction and Aim: Malaria is endemic in many parts of India. Glucose 6 phosphate dehydrogenase (G6PD) deficiency is known to protect against malaria. G6PD deficient individuals afflicted with malaria when treated with primaquine, the first line oxidant drug of malaria, encounter adverse to fatal complications due to acute precipitation of hemolytic anemia. There is a need to assess RBC indices in malaria, its implications in G6PD deficiency, and its acute manifestations. The aim of this study was to compare and correlate various RBC indices and G6PD activity in patients with and without malaria and to find a prevalence of G6PD deficiency in a tertiary care hospital.     Materials and Methods: The present study was carried out by the Biochemistry Department of Kasturba Medical College, Manipal in 363 participants (with malaria and without malaria).  Mann Whitney U test and Spearman’s Rank correlation were employed to assess group differences and correlation, respectively.   Results: 218 cases of malaria in 365 days from a tertiary care hospital in South India is an alarming incidence and annuls the fact that the malaria prevalence is relatively low in South India. Complete blood counts and red blood indices did not show any statistically significant difference between the study groups. No statistically significant correlation was found between G6PD activity and RBC indices in the present study.   Conclusion: No significant differences between hematological indicators and malaria with or without G6PD deficiency hint towards the necessity of G6PD tests for radical treatment of malaria as hematological indices are unable to predict the defective enzyme activity.