Background: Autophagy is a conserved intracellular degradation pathway essential for maintaining cellular homeostasis by recycling damaged organelles and proteins. Dysregulation of autophagy has been implicated in pregnancy-related complications such as preeclampsia and fetal growth restriction, underscoring its importance in maternal and fetal health. However, the autophagy status in the placental tissue of COVID-19-infected pregnant women remains unknown. Objective: To investigate autophagy activity in term placentas from pregnant women infected with COVID-19 compared to those from uninfected control pregnant women. Methods: In this prospective cross-sectional single-center study, 15 COVID-19-positive and 15 COVID-19-negative term pregnant women who delivered at Sultan Qaboos University Hospital between January 2020 and December 2022 were included. Immediately after delivery, the placental tissue samples were collected and assessed for autophagy activity using immunohistochemistry for LC3B and p62 markers, histopathological examination, and transmission electron microscopy. The proportion and intensity of LC3B and p62 staining were quantified. Statistical analysis was performed using the Mann–Whitney U test. Results: There was a significant reduction in p62 and LC3B expression in both the proportion and intensity in COVID-19 placentas compared to the control group. The proportion of p62 (p = 0.001) and LC3B (U = 46.000, p = 0.003) was significantly reduced in infected placentas. Similarly, intensity levels of both markers showed significant differences (p < 0.05), supporting the evidence of reduced LC3B/p62, suggesting autophagy modulation in COVID-19 patients’ placentas. Additionally, abnormal ultrastructural changes were observed in COVID-19–positive placentas, including mitochondrial injury, endoplasmic reticulum stress, microvillus loss, and basement membrane thickening. Conclusion: The study results from a limited sample size demonstrate a significantly altered autophagy flux in the placental tissues of term pregnant women with COVID-19 infection. These findings highlight the potential impact of COVID-19 infection on placental function and fetal development and underscore the need for further investigation into autophagy-modulating strategies to improve maternal–fetal health.