The COVID-19 pandemic has raised concerns about antimicrobial resistance (AMR), especially in the context of secondary bacterial infections. This study investigates the impact of SARS-CoV-2 infection on the resistome of the upper respiratory tract (URT) using a metagenomic next-generation sequencing (mNGS) approach. Samples from 48 SARS-CoV-2-infected individuals and 47 healthy individuals from Central India were analyzed to assess variations in AMR gene profiles. Our results revealed significant differences in AMR gene diversity and abundance between the two groups. SARS-CoV-2 samples exhibited greater alpha diversity (Chao1 index) and higher variability, as evidenced by PCA and PCoA analyses, which showed distinct clustering. Additionally, 24 AMR gene families were significantly more abundant in the SARS-CoV-2 group. These gene families conferred resistance against 20 different drug classes, including macrolides, beta-lactams, and aminoglycosides. Notably, AMR genes linked to ESKAPE pathogens were more prevalent in the SARS-CoV-2 group. These findings highlight the potential role of SARS-CoV-2 in driving changes in the URT resistome, with implications for managing secondary infections and guiding antibiotic stewardship in future pandemics. Keywords: SARS-CoV-2, antimicrobial resistance, resistome, upper respiratory tract, metagenomics, ESKAPE pathogens, antibiotic resistance.