Background <p>Cortisol secretion reflects hypothalamic-pituitary-adrenal axis activation during stress and illness. In children with new-onset type 1 diabetes mellitus (T1DM), diabetic ketoacidosis (DKA) and acute kidney injury (AKI) are common complications associated with metabolic stress. However, the relationship between cortisol dynamics, disease severity, and renal parameters at T1DM onset remains unclear. This study aimed to evaluate the association between cortisol levels and clinical, biochemical, and renal features in children with newly diagnosed T1DM.</p> Methods <p>This observational cross-sectional study included 153 children from the DiAKIdney cohort (2017–2019) with newly diagnosed T1DM. Serum cortisol levels were measured on the first morning after admission. Participants were stratified into three groups based on morning cortisol levels (&lt; 10, 10–18, and &gt; 18&#xa0;µg/dL). Clinical data, biochemical markers, and renal parameters were compared across groups. Associations between cortisol levels and disease severity were analyzed using multivariate analyses.</p> Results <p>Higher cortisol levels were significantly associated with greater disease severity. Patients with cortisol &gt; 18&#xa0;µg/dL exhibited more severe clinical symptoms, greater severity of DKA, and increased tubular stress. Higher cortisol levels were also strongly associated with increased risk of DKA (odds ratio = 1.12;95% CI:1.063–1.169; <i>p</i> &lt; 0.001). Conversely no significant association emerged between cortisol levels and AKI prevalence. Patients with cortisol &lt; 10&#xa0;µg/dL had milder clinical presentations without adverse outcomes.</p> Conclusions <p>Cortisol levels may serve as a practical marker of metabolic stress and risk stratification in children with new-onset T1DM, particularly in the context of DKA severity.</p> Clinical trial number <p>Not applicable.</p>