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Purpose: This study examined the effects of life stress and self-esteem on college life adjustment among health science students. Methods: A structured questionnaire was administered to students enrolled in health-related majors, and 495 valid responses were analyzed. Data were processed using SPSS version 29.0 (IBM). Statistical methods included descriptive statistics, t-tests, analysis of variance, correlation analysis, and multiple regression analysis. Results: Life stress differed significantly according to department and major satisfaction (p<0.05). Although overall life stress level was relatively low (mean [M]=2.03), academic-related stress was high (M=3.04). Self-esteem showed significant differences by grade level, department, motivation for major selection, and major satisfaction (p<0.05), with a relatively high average score (M=3.72). College life adjustment also differed significantly according to department, motivation for major selection, and major satisfaction (p<0.05), and demonstrated a relatively high overall mean (M=3.40). Life stress was negatively correlated with college life adjustment, whereas self-esteem was positively correlated. Multiple regression analysis demonstrated that academic stress, value-related stress, and stress related to relationships with professors negatively influenced college life adjustment, whereas selfesteem had a significant positive effect. Conclusion: Life stress and self-esteem were identified as key factors influencing college life adjustment among health science students. These findings highlight the need for comprehensive psychological support programs focused on mitigating stress and boosting selfesteem to promote successful adjustment to college life.