Background: Increased occurrence of mucormycosis in India during the second wave of the COVID-19 pandemic in early 2021 in India subsequently prompted us to undertake a multi-site case-control investigation. The objectives were to examine the monthly trend of Covid-19 Associated Mucormycosis (CAM) cases among in-patients and to identify factors associated with it.Methods: Eleven study sites were involved across India and archived records since 1st January till 30th September, 2021 were used for trend analysis. The cases and controls were enrolled during 15th June 2021 to 30th September 2021. Data were collected using a semi-structured questionnaire. Among 1211 enrolled participants, 336 were CAM cases and 875 were COVID-19 positive non-mucormycosis controls. Results: Admitted CAM-case number reached highest point in May 2021 after a month of peak admission for COVID-19. Odds of developing CAM increased with the history of working in a dusty environment (adjusted odds ratio; aOR 3.24, 95%CI: 1.34, 7.82), diabetes mellitus (aOR: 31.83, 95%CI: 13.96, 72.63), longer duration of hospital stay (aOR: 1.06, 95%CI: 1.02, 1.11) and use of methyl prednisolone (aOR: 2.71, 95%CI: 1.37, 5.37) following adjustment for age, gender, occupation, education, type of houses used for living, requirement of ventilatory support and route of steroid administration. Higher proportion of CAM cases required supplemental oxygen compared to the controls; use of non-rebreather mask (NRBM) was associated as a protective factor against mucormycosis compared to face masks (aOR: 0.18, 95%CI: 0.08, 0.41). Genomic sequencing of archived respiratory samples showed similar presence of Delta and Delta derivates in both cases and controls.Conclusions: Appropriate management of hyperglycemia, judicious use of steroids and use of NRBM during oxygen supplementation among COVID-19 patients bear the potential to reduce the risk of occurrence of mucormycosis. Avoiding exposure to dusty environment would add to prevention efforts.