The purpose of this study was to explore the psychological mechanisms of how perceived autonomy support by the principal affects positive and negative aspects of teachers' well-being. While satisfaction of the basic psychological needs (Deci and Ryan in Psychol Inquiry 11:227-268, 2000, https://doi.org/10.1207/S15327965PLI1104_01; Ryan and Deci in Am Psychol 55:68-78, 2000, https://doi.org/10.1037/0003-066x.55.1.68) has already been shown to mediate this relationship (Klassen at al. in J Educ Psychol 104:150-165, 2012, https://doi.org/10.1037/a0026253), we examined need frustration and need satisfaction separately as possible differential mediators. Participants were secondary level teachers (N = 49) who completed a questionnaire on perceived autonomy support by the principal, need satisfaction, need frustration, life satisfaction, positive affect, negative affect, and emotional exhaustion. Parallel multiple mediation analyses show that on the one hand, only need satisfaction, in particular autonomy satisfaction, mediates between autonomy support and positive affect. On the other hand, only need frustration of each of the three needs is a mediator for negative affect and emotional exhaustion. However, both frustration and satisfaction of the need for autonomy mediate between autonomy support and life satisfaction. The results of this study emphasize the benefits of examining teachers' need satisfaction and need frustration as distinct psychological processes in order to more adequately understand how the social context affects teachers' well-being. Specifically, the role of need frustration should be considered in explaining teachers' high ill-being. Thus, this study provides implications for fostering teachers' health, on a school level by sensitizing principals for autonomy-supportive leadership and on an individual level by developing teachers' coping skills for experiences of need frustration.