Nursing students often face high academic and emotional demands, which can negatively affect both their mental health and academic performance. From a salutogenic perspective, the sense of coherence (SOC) is considered a key protective factor in managing stress and fostering resilience. : This study aimed to explore the SOC levels among nursing students and examine their associations with perceived academic stress and sociodemographic variables. : A multicenter, cross-sectional, exploratory study was conducted in a sample of 1301 undergraduate nursing students from four universities in Spain and Chile. Participants completed the Orientation to Life Questionnaire, a validated instrument assessing SOC and its three dimensions: comprehensibility, manageability, and meaningfulness. Sociodemographic data and students' perceived stress in relation to key academic activities were also collected. Descriptive and inferential statistical analyses were performed, including -tests and ANOVA. : The mean SOC score was 62.65 (SD = 12.36), with no significant differences between universities. Significant associations ( < 0.05) were found between SOC scores and age, marital status, academic year, work status, and university entry path, but not with gender or caregiving responsibilities. Students aged ≥29 years and those who were married or working had higher SOC scores. Higher levels of perceived stress in lectures, seminars, clinical practice, group work, and written assignments were significantly associated with lower SOC scores. : This study's findings suggest that a stronger SOC is associated with lower perceived academic stress and certain sociodemographic characteristics. Integrating salutogenic approaches into nursing curricula could strengthen students' SOC, promoting their mental well-being and academic resilience.