The current study sought to explore the associations between migration-related stress and the mental health of migrant children coming from Central America and Mexico who were held in United States immigration detention facilities during the summer of 2019. Increasing numbers of family units have been migrating to the United States since 2014, with an especially steep increase in 2019. Migration is a complex and inherently stressful experience that is known to confer risk for development of posttraumatic stress disorder (PTSD) and other psychiatric disorders. Increasing amounts of time in immigration detention is shown in other populations to exacerbate this effect. Due to heightened plasticity of the developing brain, migration-related trauma may have a particularly strong impact on mental health in children and adolescents. Recent shifts in United States immigration policy in 2018 led to increases in separation of migrant children from their parents upon entry into the United States. Growing evidence across species suggests that caregivers play a central role in moderating the effects of traumatic stress on children’s brain development and physiological responsivity to stress, including buffering children from the detrimental neurobiological effects of stress. We hypothesized that children’s separation from parents and/or length of detention would exacerbate the effect of immigration stress on psychiatric outcomes, specifically the presence and severity of PTSD. We conducted 65 interviews with monolingual Spanish-speaking parents of 84 migrant children (ages 1-17) originating from Honduras (n = 37), El Salvador (n = 20), Mexico (n = 9), Guatemala (n = 8), and Nicaragua (n = 2), currently one of the most violent regions in the world. Interviews were conducted in shelters within 1-2 days after families were released from detention facilities in Texas. A modified version of the UCLA Posttraumatic Stress Disorder Reaction Index (UCLA PTSD RI) was administered to assess for trauma exposure that occurred before, during, and after migration, and a semi-structured interview was conducted to assess family demographics and children’s migration- and detention-related experiences. Regression analyses controlling for child age revealed a significant interaction between children’s pre-immigration trauma and length of detention predicting children’s PTSD symptom severity. Results underscore the negative effects of immigration detention on Central American and Mexican children’s mental health outcomes and suggest that children’s pre-immigration trauma may make children more vulnerable to the effects of migration-related stress on mental health outcomes.