<p>Red blood cell distribution width (RDW) can be employed to prognosticate the outcome of adult patients infected with 2019-nCoV and to appraise the efficacy of treatments for neonatal sepsis. Nevertheless, its utilization in neonates infected with 2019-nCoV remains unexplored. In this research, we examine the association between RDW and 2019-nCoV infection in neonates and its potential as an indicator of therapeutic efficacy. The clinical and laboratory data of neonates diagnosed with 2019-nCoV infection or sepsis in the neonatal intensive care unit (NICU) of two hospitals were gathered and retrospectively analyzed via a sample t-test. The RDW of the neonatal 2019-nCoV infection group was lower than that of the neonatal sepsis group (<Emphasis Type="BoldItalic">P</Emphasis> &lt; 0.05). In each group, the RDW following treatment was lower than that before treatment (<Emphasis Type="BoldItalic">P</Emphasis> &lt; 0.05). These outcomes suggest that the alterations in RDW in neonates with 2019-nCoV infection exhibit smaller overall fluctuations compared to those with neonatal sepsis. However, they are equally effective in evaluating treatment efficacy, with notable improvement detected after therapy. Our discoveries broaden the application of RDW in neonates with 2019-nCoV infection and imply that the dynamic changes in RDW can be utilized to assess the therapeutic effect.</p>