Emerging evidence suggests the coronavirus disease 2019 (COVID-19) pandemic is adversely affecting adolescents' mental health and health behaviors, particularly among those with preexisting mental health conditions and from lower socioeconomic backgrounds. However, direct tests of changes in health outcomes among vulnerable adolescents from before to during COVID-19 are limited. In addition, little is known about how to buffer adolescents, particularly those who are most vulnerable, against stress-related decrements in health. This randomized controlled trial begins to fill these gaps in the literature by exploring changes in mental health, health behaviors, executive function, emotion regulation, and mindfulness among vulnerable adolescents involved in a mentoring program during the COVID-19 pandemic. It also examined to what extent there were protective benefits of incorporating mindfulness training within a mentoring program for buffering adolescents from negative pandemic health effects. Thirty-five adolescents (M[subscript age] = 12.9, 37% female) and 32 parents (M[subscript age] = 44.75, 80% female) completed questionnaires at baseline (February 2020) and follow-up (July 2020). There were few significant reductions in health; instead, on average, youth reported improvements in sleep, emotion regulation, executive function, and mindfulness over time. Adolescents randomized to mentoring + mindfulness displayed significantly less posttraumatic stress disorder (PTSD) symptomatology and emotional impulsivity at follow-up, compared to the mentoring-as-usual condition. These pilot findings suggest that mentoring with a mindfulness training component may offer an effective strategy for protecting adolescents from deteriorations in health outcomes during COVID-19. Further, there may be unique benefits of mindfulness training for vulnerable youth as a way to adapt to stressful events.