Background <p>Nutritional status is associated with clinical outcomes in COVID-19 patients. The aim of this study was to investigate the relationship between the prognostic nutritional index (PNI) and adverse prognosis outcomes in COVID-19 patients.</p> Methods <p>In this study, 1190 patients with COVID-19 who were hospitalized at the Affiliated Hospital of Guangdong Medical University from December 2022 to March 2023 were selected. Multivariate logistic regression analysis model was employed to assess the relationship between the PNI and prognosis outcomes. Restricted cubic spline (RCS) curves were used to evaluate the risk ratio of adverse prognosis outcomes with continuous PNI. The predictive accuracy of these risk factors was assessed by Receiver Operating Characteristic (ROC) curves. Finally, subgroup analysis was used to evaluate the robustness of the test results.</p> Results <p>This study encompassed a cohort of 1,117 subjects. Stratification by PNI quartile revealed an increased incidence of negative prognostic indicators in the lowest quartile (Q1: 174 [62.1%] versus Q2: 119 [43%] versus Q3: 78 [27.9%] versus Q4: 44 [15.7%], <i>P</i> &lt; 0.001). Multivariate logistic regression analysis, with adjustment for potential confounders, demonstrated that the PNI was a significant independent predictor of negative prognostic outcomes (odds ratio [OR] = 0.95, 95% confidence interval [95% CI]: 0.93–0.97, <i>P</i> &lt; 0.001). The RCS curve demonstrated this relationship, with the PNI below 40 associated with an increased risk of adverse prognostic outcomes. The area under the ROC curve (AUC) values were 0.722 (95%CI: 0.691–0.752) for PNI, with a cutoff of 39.3, yielding a sensitivity of 0.671 and a specificity of 0.661.</p> Conclusions <p>This study reveals that PNI is an independent predictor of adverse prognosis outcomes in COVID-19 patients. A higher PNI may be associated with a lower risk of COVID-19 disease progression.</p> Clinical trial number <p>Not applicable.</p>