The COVID-19 pandemic has continued from 2019 to current times, exacerbating existing epidemics since its beginning. Pathologic lung lesions in acute cases have consisted of hyaline membrane disease and microthrombi. More severe cases have pathologic lesions of alveolar and bronchiolar epithelial necrosis, lymphocytic interstitial infiltrate, and peribronchiolar and perivascular lymphocytic infiltrate. The opioid epidemic is one epidemic exacerbated by COVID-19. Those with opioid use disorder (OUD) are more likely to have compromised lung function, of which infection with the SARS-CoV-2 virus can worsen. The combined symptoms lead to an increased risk of overdose. In addition to anatomical risks, those with OUD require person-to-person contact to obtain opioids. This enhances the spread of COVID-19 and increases the risk of acquiring the disease. Pathological findings in those with chronic OUD can contain fluorescing talc powder with multinucleated giant cells and granulomas in the lung tissue. Twenty-one positive cases and twenty-two negative cases were collected from COVID-19 suspicious decedents in Marion County Coroner’s Office. Toxicology screens and COVID-19 RT-PCR tests were run on each of the 43 decedents. Microscopic evaluation was done by hematoxylin and eosin (H & E) and Masson’s Trichrome stains. The age range of those collected was 3 to 81 years. The ethnicities were 1 Asian, 8 African American, 1 Cuban, 3 Hispanic, 29 Caucasian, and 1 unknown. The male to female ratio was 3.8:1. The histological features found in this study were alveolar and bronchiolar epithelial necrosis, lymphocytic interstitial infiltrates, perivascular and peribronchiolar lymphocytic infiltrate, fibrosis, microthrombi, and hyaline membrane. Fluorescing talc was seen in 5 cases with granulomas and multinucleated giant cells. Toxicology reports showed 11 drug-related deaths, with cocaine, methamphetamine, alcohol, fentanyl, morphine, acetyl fentanyl, and sertraline as the causative agents.