This cross-sectional study aimed to determine the factors affecting stress in high school students. The sample participants were 365 high school students in Phitsanulok Province selected by stratified random sampling. Data were collected by a self-administered questionnaire consisting of 6 parts: 1) socio-demographic characteristics; 2) lifestyle factors; 3) disease prevention motivation; 4) social support; 5) stress prevention behaviors, and 6) stress. Frequency, percentage, mean, standard deviation, and binary logistic regression were used for data analysis. All significance levels were set at 0.05. The results showed that 72.9% of the sample participants were female and 75.10% had stress. Female students were more likely to experience stress than male students (ORadj = 1.902; 95%CI: 1.117 - 3.241). Excessive expenses possibly caused stress (ORadj = 3.618, 95%CI = 1.031-12.694). The students with intermediate resilience faced greater stress than those with extraordinary strength (ORadj = 3.198; 95%CI: 1.957 – 5.224). The sample participants who received mild and average social support tended to experience greater stress than those with higher levels of social support (ORadj = 4.762, 95%CI = 1.012-22.412, OR = 2.036, 95%CI = 1.155-3.589). This study suggests that related institutes strengthen living skills and improve social support for high school students to prevent severe stress.