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Post-renal transplant patients are at higher risk of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) infection due to suppressed immune system, underlying co-morbidities and antimetabolites used to prevent graft rejection. Cytomegalovirus infection causes memory inflation and further alters the clinical outcome. We report a case of severe COVID-19 in a post-renal transplant patient co-infected with cytomegalovirus and challenges in its management. The use of conventional protocol for treatment is a matter of concern in view of the complex clinical profile in them. Thus, it requires a multidisciplinary approach and individualization of the therapy to attain a fine balance between risk of graft rejection and complications of overimmunosuppression especially during cytokine storm. This brings us to explore other treatment modalities like cytosorb and plasmapheresis to prevent systemic inflammation in body while also targeting the cytomegalovirus infection.