Stress, and stress-related health complaints, are common among young people, especially girls. Since studies have shown that school demands are an important driver of stress in adolescents, identifying if school-based resources can protect against stress is highly relevant. The aim of this study was to analyse task-related demands and task-related coping resources as aspects of the school work environment of potential relevance for stress in mid-adolescent girls and boys. The data came from “The School Stress and Support study” (TriSSS) conducted among students in grades 8 and 9 (aged 14–16 years). Self-reports of demands, coping resources, stress, as well as recurrent pain, were collected through questionnaires (n = 411). A subsample of students (n = 191–198) also provided salivary samples, which were analysed for the stress marker cortisol. Linear (OLS) and binary logistic regression analyses showed that higher demands were associated with more perceived stress, a higher likelihood of recurrent pain, and a lower cortisol awakening response. Greater coping resources were associated with less perceived stress and a lower likelihood of recurrent pain, but there was no association with cortisol. The strength of the associations differed by gender. The findings suggest that schools can promote student wellbeing by providing clear and timely information and teacher support to the students, especially for boys. Identifying specific features of the schoolwork that give rise to stress and to modify these accordingly is also of importance, especially for girls.