Background: This study investigated the role of genetic polymorphisms in IFNAR2, OAS1, OAS3, and ACE2 as predictors of Paxlovid treatment response, specifically examining their influence on the clinical course and laboratory parameters of COVID-19 patients. Methods: We analyzed the impact of polymorphisms in genes associated with the interferon pathway (IFNAR2 rs2236757), antiviral response (OAS1 rs10774671, OAS3 rs10735079), and viral entry (ACE2 rs2074192) in individuals treated with Paxlovid. Results: Our findings suggest that genetic variations in these genes may modulate the immune response and coagulation pathways in the context of Paxlovid treatment during COVID-19 infection. Specifically, the IFNAR2 rs2236757 G allele was associated with alterations in inflammatory and coagulation markers, while polymorphisms in OAS1 and OAS3 influenced coagulation parameters. Furthermore, specific genotypes were linked to changes in clinical parameters such as oxygen saturation, leukocyte count, and liver function markers in Paxlovid-treated patients. Conclusions: These results highlight the potential of considering genetic factors in understanding individual responses to COVID-19 treatment with Paxlovid and informing future personalized approaches.