Abstract The non-protein calorie-to-nitrogen ratio (NPC/N, kcal/g) is recognized as a valuable metric for assessing the balance between non-protein energy intake and nitrogen derived from protein. This study aimed to investigate the association between NPC/N and mortality among overweight and obese adults. Data were obtained from the National Health and Nutrition Examination Survey (1999–2018), with mortality follow-up through December 31, 2019.