The aim of this study was to evaluate the effect of an intervention with a universal program (single-tier) in one group, and the combination of this universal program and a selected + indicated measure (multi-tier) in another group. Interventions were designed to enhance the psychosocial environment to reduce loneliness and mental health problems. 17 upper secondary schools in Norway were randomly assigned with six, six, and five schools in the single-tier, multi-tier and control group respectively. An overall increase in mental health problems and loneliness was found in all groups at follow-up. Compared to girls in the control group, girls in the multitier group had a significantly lower increase in mental health problems. Due to small effects, we take caution in interpreting findings.