Background <p>School-weariness (SW) is a pattern of persistent negative affect toward learning and school, with cognitive devaluation of academic activities. SW is associated with reduced academic motivation, poorer academic functioning, and internalizing/somatic problems, but its cognitive-affective processes and autonomic correlates remain unclear. This study examined whether SW is associated with enhanced emotional Stroop interference and selective physiological differences in junior middle school students.</p> Methods <p>This exploratory cross-sectional matched case–control study recruited 47 junior middle school students from three schools in Hangzhou, China. Participants completed questionnaires and an emotional Stroop task with electrocardiographic recording during baseline, task, and recovery. Behavioral outcomes were analyzed using linear mixed-effects models or binomial generalized linear mixed-effects models, and electrocardiography (ECG) / heart rate variability (HRV) outcomes were analyzed using linear mixed-effects models. Age, gender, and school source were included as covariates where appropriate.</p> Results <p>Compared with controls, the SW group showed higher scores in all symptom scales, slower reaction times, and greater emotional Stroop interference. Accuracy effects were not significant. For the ECG results, the SW group showed higher heart rate across baseline, task, and recovery. The HRV measures showed no robust group-related pattern.</p> Conclusions <p>SW in junior middle school students was characterized by greater internalizing/somatic burden, slower responding, and greater interference from school-related negative words, together with limited exploratory autonomic differences.</p>