Background <p>Nursing students experience high prevalence of depression, anxiety, and stress, but traditional variable‑centered approaches may overlook distinct subgroups. This study aimed to identify homogeneous profiles of affective distress and examine their related factors.</p> Methods <p>Nursing students (<i>n</i> = 1184) from five medical colleges in Sichuan Province, China were recruited from March 3 to May 30, 2025. Participants were asked to complete questionnaires regarding depression, anxiety and stress, social emotional competency and alexithymia. Latent profile analysis (LPA) was used to identify depression, anxiety, and stress profiles. Chi-square tests and one-way analysis of variance (ANOVA) were used to examine differences in characteristics. Multivariate logistic regression analysis was conducted to explore related factors.</p> Results <p>The prevalence of depression, anxiety, and stress among nursing students were 38.52%, 46.12%, and 22.47%, respectively. LPA revealed three distinct profiles: “severe affective distress” (11.06%), “moderate affective distress” (35.14%), and “mild affective distress” (53.80%). Related factors for depression, anxiety, and stress included social emotional competency, alexithymia, gender, parenting style, monthly family income, professional identity, satisfaction with campus life, adverse childhood experiences, and campus bullying.</p> Conclusions <p>To our knowledge, limited research has applied LPA to examine depression, anxiety, and stress among nursing students. This study identified three distinct latent profiles, revealing significant heterogeneity influenced by individual, family, academic, traumatic characteristics, while social emotional competency and alexithymia. The identified associated factors, including modifiable characteristics such as social emotional competency, alexithymia, campus environment, and bullying, may inform future targeted interventions.</p> Clinical trial number <p>Not applicable.</p>