India is experiencing a second wave of COVID-19, with 28.2 million cases reported as of this writing, although this is likely an underestimate; the true toll is estimated at more than 500 million cases. The unprecedented increase in COVID-19 cases during this second wave exposed the crippled health care system. Oxygen supplies have dwindled, hospitals have turned away patients because of a lack of beds, and shortages of critical medicines have occurred. In the midst of this crisis, a “syndemic” of rhino-orbito-cerebral mucormycosis infections has arisen, with nearly 9000 cases reported so far from several states in India. A syndemic recognizes the interactions between social and biological factors that result in more adverse disease outcomes. Compounding the crises are reported shortages of amphotericin B, the main drug used to treat mucormycosis. Although COVID-19–associated mucormycosis is not unique to India, emerging data indicate that the extraordinarily high prevalence is multifactorial, with contributions from poorly controlled diabetes, excessive use of corticosteroids and possibly antibiotics, and environmental exposure.