The present study was carried out with the objectives of genotyping Pneumocystis jirovecii at three distinct loci, to identify the single nucleotide polymorphisms (SNPs), and to study its clinical implications in patients with Pneumocystis pneumonia (PCP). Analysis of genetic diversity in P. jirovecii from immunocompromised patients was carried out by genotyping at three distinct loci encoding mitochondrial large subunit rRNA (mtLSU rRNA), cytochrome b (CYB), and superoxide dismutase (SOD) using polymerase chain reaction (PCR) assays followed by direct DNA sequencing. Of the 300 patients enrolled in the present study, 31 (10.33%) were positive for PCP by a specific mtLSU rRNA nested PCR assay, whereas only 15 P. jirovecii could be amplified at the other two loci (SOD and CYB). These positives were further subjected to sequence typing. Important genotypic combinations between four SNPs (mt85, SOD110, SOD215, and CYB838) and clinical outcomes could be observed in the present study, and mt85A, mt85T, and SOD110C/SOD215T were frequently associated with "negative follow-up". These SNPs were also noted to be relatively more prevalent amongst circulating genotypes in our study population. The present study is the first of its kind from the Indian subcontinent and demonstrated that potential SNPs of P. jirovecii may possibly be attributed to the clinical outcome of PCP episodes in terms of severity or fatality in different susceptible populations likely to develop PCP during their course of illness.