Millions of Americans infected with the severe acute respiratory syndrome-associated coronavirus-19 (COVID-19) need oncologic surgery. Patients with acute or resolved COVID-19 illness complain of neuropsychiatric symptoms. How surgery affects postoperative neuropsychiatric outcomes such as delirium is unknown. We hypothesize that patients with a history of COVID-19 could have an exaggerated risk of developing postoperative delirium after undergoing major elective oncologic surgery. We conducted a retrospective study to determine the association between COVID-19 status and antipsychotic drugs during postsurgical hospitalization as a surrogate of delirium. Secondary outcomes included 30 days of postoperative complications, length of stay, and mortality. Patients were grouped into pre-pandemic non-COVID-19 and COVID-19-positive groups. A 1:2 propensity score matching was used to minimize bias. A multivariable logistic regression model estimated the effects of important covariates on the use of postoperative psychotic medication. A total of 6003 patients were included in the study. Pre- and post-propensity score matching demonstrated that a history of preoperative COVID-19 did not increase the risk of antipsychotic medications postoperatively. However, respiratory and overall 30-day complications were higher in COVID-19 individuals than in pre-pandemic non-COVID-19 patients. The multivariate analysis showed that the odds of using postoperative antipsychotic medication use for the patients who had COVID-19 compared to those who did not have the infection were not significantly different. A preoperative diagnosis of COVID-19 did not increase the risk of postoperative antipsychotic medication use or neurological complications. More studies are needed to reproduce our results due to the increased concern of neurological events post-COVID-19 infection.