Experiencing school burnout symptoms can have negative consequences for learning. A growth mindset, the belief that human qualities such as intelligence are malleable, has previously been correlated with fewer school burnout symptoms in late adolescents. This might be because adolescents with a stronger growth mindset show more adaptive self-regulation strategies and thereby increasing resilience against academic setbacks. Here we confirmed in a sample of 426 Dutch young adolescents (11–14 years old; 48% female) that this relationship between growth mindset and school burnout symptoms holds after controlling for other potential predictors of school burnout symptoms such as academic achievement, school track, gender, and socio-economic status. Our second aim was to increase our understanding of the mechanism underlying the relation between mindset and school burnout, by measuring physiological resilience (vagal activity, a measure of parasympathetic activity, also known as heart rate variability or HRV) in a subsample (n = 50). We did not find any relation between vagal activity and growth mindset or school burnout symptoms, nor could we establish a mediating effect of vagal activity in their relation. In conclusion, we found evidence for a potential protective effect of a growth mindset on school burnout symptoms in young adolescents, but not for physiological resilience (vagal activity) as an underlying mechanism. The protective effect of growth mindset as confirmed in our younger sample can be leveraged in interventions to prevent increasing school burnout symptoms.