AbstractBackground: India launched the National Framework for Malaria Elimination to encourage surveillance and strategies towards ‘elimination’ rather than control by 2030. Considering the significant challenges on this path, regional variations in clinical and haematological manifestations are useful parameters to help shape national elimination strategies. Our study aims to compare the demographic, clinical and haematological parameters among severe malaria cases and highlight mixed malaria infection. Methods: A cross sectional study was carried out between January 2015 and May 2018. Diagnosis was done by peripheral smear microscopy, followed by immunochromatographicrapid test and finally quantitative buffy coat test. Patients were classified as severe and non-severe disease according to WHO major criteria. The relevant data of the study subjects was collected from inpatient case records and analysed. Results: A total of 403 inpatients with confirmed malaria were included in our study. Severe malaria was observed in 21.5% and these patients had a significantly longer stay in hospital of 6.08 ± 3.78 days. Infections caused by P. falciparum (48.6%) and P. vivax (46.9%) were almost equal in number. Acute respiratory distress syndrome was observed more in 21.4% (9/42) of P. vivax infections. Mixed malarial infections were observed in 4.5% (18/403) of total patients and 33% of mixed malarial cases presented with severe manifestations. Conclusions: Attributing severe malaria to P. falciparum or P. vivax alone can be misleading especially in regions with complicated epidemiology, like India. Identification of malarial coinfectionsinfection are difficult without molecular diagnostic tools. Incorrect diagnosis may directly affect appropriate antimalarial therapy selection. Highlights • Clinical and haematological manifestations have not been observed as a malaria burden metric in all regions. • Identification of malarial coinfectionsinfection are difficult without molecular diagnostic tools. • Appropriate laboratory diagnosis of mixed malarial infections aids in selecting antimalarial therapy. • Study of regional variations in malaria presentations can improve public health. Keywords: Malaria co-infection; Plasmodium; India; Endemic; Eradication.