Background <p>The SARS-CoV-2 remains prevalent, and neonates remain susceptible. This study aims to explore the potential of the Neutrophil-to-Lymphocyte Ratio (NLR) as a valuable tool for assessing the severity of SARS-CoV-2 infection in term neonates in the late neonatal period (8–28 days of life). Additionally, it seeks to examine the underlying immune characteristics associated with this ratio.</p> Methods <p>A retrospective cohort study was conducted from November 1, 2022, to February 1, 2023 in four hospitals. Baseline characteristics and laboratory results were collected and analyzed. Receiver operating characteristic (ROC) curve of NLR and lymphocyte subsets analysis were performed.</p> Results <p>The study enrolled 143 term neonates in the late neonatal period with confirmed SARS-CoV-2 infection, comprising 54 severe cases and 89 non-severe cases, along with 59 age-matched uninfected controls. The NLR was identified as an associated factor for severe SARS-CoV-2 in term neonates in the late neonatal period. Furthermore, the levels of CD4+CD45RA and CD8+CD28+ T cells were significantly reduced in neonates with SARS-CoV-2 compared to healthy neonates, and a significant decrease in CD8+CD28+ T cells was observed in the severe SARS-CoV-2 group compared to the non-severe group. </p> Conclusions <p>NLR is an associated factor of severe SARS-CoV-2 in term neonates in the late neonatal period. The pathogenicity of severe SARS-CoV-2 infection in term neonates in the late neonatal period may be related to alterations in lymphocyte subsets</p> Clinical trial <p>Not applicable.</p>