Aims: The study was aimed to evaluate the effect of prosthodontic rehabilitation on psychological status (PS) and quality of life (QoL) in maxillectomy patients of coronavirus disease 2019-associated mucormycosis (CAM). Settings and Design: The study was designed as a prospective and clinical study. Materials and Methods: Twenty-four CAM patients undergoing maxillectomy and subsequent prosthetic rehabilitation were included. The treatment involved surgical, intermediate, and definitive obturator delivery at various phases of healing. PS was assessed using the Hospital Anxiety and Depression Scale (HADS), QOL using the European Organization for Research and Treatment of Cancer QoL Questionnaire-Head and Neck Module (EORTC QLQ-HandN35), and the functioning of obturator was assessed utilising the Obturator Functioning Scale (OFS) at various time points: before maxillectomy (T1), 2 weeks after maxillectomy (T2), 2 weeks upon usage of intermediate obturator (T3), just before delivery of definitive obturator (T4), and 12 weeks after the usage of definitive obturator (T5). Statistical Analysis Used: Data were analyzed using a social science statistical analysis program (Stata 14.0; StataCorp LLC, Texas, USA). The significance level was chosen <0.05. Shapiro–Wilk test was used to assess the normality of quantitative data. Student’s t-test was employed (α =0.05) to evaluate if the patient’s PS, QOL, and obturator function had changed over time. The Spearman correlation coefficient (α =0.05) was utilized to evaluate the correlation coefficient between PS, QOL, and obturator function seen at T3 and T5. Results: Out of 24 enrolled patients, nine were dropped out. HADS-anxiety score was the highest at T1 (18.6 ± 1.2) and HADS-depression score was the highest at T2 (18.8 ± 1.6). HADS scores decreased significantly (P = 0.001) after prosthetic rehabilitation. EORTC QLQ-HandN35 score was the highest at T2 (105.8 ± 29.5), with statistical significance (P = 0.001) after rehabilitation. OFS was the highest at T3 (51.9 ± 3.9) and lowest at T5 (25.4 ± 2.8). Conclusion: CAM and maxillectomy deliberately affects the PS and QOL. Prosthetic rehabilitation, psychological motivation, and education create greater improvement in PS and QOL. The progress in parameters showed an upward trend with good obturator quality over a period of time.