Background: Both depressive disorder and subclinical depressive symptoms during adolescence are a major public health concern. Therefore, it is important that depression is detected at an early stage and is treated preventively. Prevention based on the principles of Cognitive Behavioural Therapy (CBT) has proven to be the most effective, however research has mainly focused on the effectiveness of "prevention packages" consisting of multiple CBT-components, rather than on the distinct CBT-components. This study will evaluate the relative effectiveness of four core components of CBT (cognitive restructuring (CR), behavioural activation (BA), problem solving (PS) and relaxation (RE)). In addition the relative (cost-)effectiveness of four different sequences of these components will be evaluated: (1) CR - BA - RE - PS, (2) BA - CR - RE - PS, (3) PS - GA - CR - RE and (4) RE - PS - BA - CR. Methods: We will perform a non-blinded multisite cluster randomized prevention microtrial with four parallel conditions consisting of the four sequences. The four sequences of components will be offered in groups of high school students with elevated depressive symptoms. For each CBT-component a module of three sessions is developed. Assessments will be conducted at baseline, after each CBT-component, prior to each session, at post-intervention and at 6-month follow-up. Potential moderators and mediators will be evaluated exploratively to shed light on for whom the (sequences of) CBT-components are most effective and how effects are mediated. Discussion: The potential value of the study is insight in the relative effectiveness of the four most commonly used CBT-components and four different sequences, and possible moderators and mediators in the prevention of depression among adolescents. This knowledge can be used to optimize and personalize CBT-programs. Trial registration: The study is registered in the Dutch Trial Register (Trial NL5584 / NTR6176) on October 13, 2016.