Background <p>Acute skin failure (ASF) is an understudied complication in patients with septic shock, and existing predictive models lack disease-specific variables. This study aimed to investigate the characteristics of cutaneous manifestations in patients with septic shock and to identify potential biomarkers and predictive factors for cutaneous deterioration.</p> Methods <p>This retrospective cohort study analysed 154 adult patients with septic shock, defined according to the Sepsis 3.0 criteria, who were admitted to a tertiary intensive care unit (ICU) between September 2020 and September 2022. Based on cutaneous manifestations observed during hospitalisation, the patients were stratified into two groups: the ASF group and the non-ASF group. Clinical characteristics, therapeutic interventions and laboratory parameters were evaluated. Significant univariate predictors were included in multivariable logistic regression. A p-value below 0.05 was considered statistically significant.</p> Results <p>This study enrolled a total of 154 patients with septic shock, among whom 49 developed ASF, yielding an incidence rate of 31.8%. In the multivariate analysis, four independent predictors were identified: maximum norepinephrine (NE) dose (odds ratio [OR] = 2.47, <i>p</i> = 0.051), NE duration (OR = 1.19, <i>p</i> = 0.054), central venous oxygen saturation (ScvO₂) (OR = 0.97, <i>p</i> = 0.042) and absence of oedema (OR = 0.18, <i>p</i> = 0.008). The model achieved an area under the curve of 0.803 (95% CI: 0.730–0.876) with 72.3% sensitivity and 72.4% specificity at the optimal cut-off.</p> Conclusions <p>The validated prediction model identifies patients with septic shock who are at high risk for ASF using four readily available clinical parameters: maximum NE dose, NE duration, ScvO₂ and absence of oedema, helping clinicians provide early warning and thereby reduce associated skin complications.</p> Clinical trial number <p>Not applicable.</p>