OBJECTIVES: In the early stages of various critical infections and diseases, altered association of cortisol and adrenocorticotropic hormone (ACTH) levels occurs, with cortisol levels increasing and ACTH levels remaining normal or decreasing. This study aimed to explore the relationship between ACTH and cortisol levels in patients with diabetic ketoacidosis (DKA) and the influence of the severity of DKA. METHODS: A total of 106 type 2 diabetes patients with DKA admitted to the Endocrinology Department of Yantai Yuhuangding Hospital from February 2018 to May 2023 were divided into groups without (n=54) and with bacterial infection (n=52). Twenty type 2 diabetes patients without infection or DKA admitted during the same period were included as the control group. Cortisol and ACTH levels were measured on the first day of admission and the day after DKA correction for patients with DKA and on the first day of admission and the day before discharge for the control group. RESULTS: Compared with the control group, the DKA groups both with and without infection had significantly higher cortisol levels ( CONCLUSIONS: In the early stage of DKA, a phenomenon of altered association between cortisol-ACTH occurs and is especially prominent in DKA patients with infection. This altered association between cortisol-ACTH disappears after DKA correction, and the severity of DKA is an independent influencing factor on the cortisol level in early-stage DKA.