Background Cytokine storm syndrome is a cascade of intensified immune responses disposing the immune system to exhaustion, which might eventually result in organ failure and fatal respiratory distress. Infection with severe acute respiratory syndrome-coronavirus-2 results in uncontrolled production of cytokines and eventually the development of cytokine storm syndrome. Clinical intervention in patients with SARS has demonstrated upregulation of cytokine production in patients with prolonged fever. Such an association between fever and cytokine storm is studied in the present research which is a hospital-based case-control study of COVID-19 patients. To the best of our knowledge, the present study is the first study of Indian population, which highlights the link between prolonged fevers, Lymphocyte count and cytokine profile in patients with the COVID-19 disease. Methods- We conducted a hospital-based case–control study of patients admitted for COVID-19 with prolonged fever and short duration of fever with a positive SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR).All the patients underwent investigationswhich includes HRCT chest, Complete Blood Count (CBC), Renal and liver panel, C- Reactive Protein (CRP), Lactate dehydrogenase (LDH), Interleukin-6 (IL-6) and Ferritin, as a part of their COVID-19 protocol clinical laboratory findings at regular intervals till discharge. Conclusions-The study reported that prolonged fever i.e. fever > 7 days from beginning of illness was associated with increased risk of cytokine storm from COVID-19 than patients with short duration of fever.There was also a marked reduction in Lymphocyte count with increased levels of inflammatory markers and fever, which is again considered an indicator of poor prognosis. The study concludes that prolonged fever should be considered as one of the earliest markers for predisposing the patient to the cytokine storm. These early signs if diagnosed correctly right at the inception of complications the further progression of cytokine storm could be avoided.Which can minimize the mortality and foster the chances of the patient’s recovery from this deadly disease