BackgroundClinically significant psychological distress in pregnancy is common, with epidemiological research suggesting that between 15 and 25 % of pregnant women experience elevated symptoms of stress, anxiety, and depression. Untreated psychological distress in pregnancy is associated with poor obstetrical outcomes, changes in maternal physiology, elevated incidence of child physical and psychological disorders, and is predictive of maternal postpartum mood disorders. Despite the wide-ranging impact of antenatal psychological distress on mothers and their children, there is a gap in our knowledge about the most effective treatments that are available for psychological distress experienced in pregnancy. Additionally, no trials have focused on potential physiological changes that may occur as a result of receiving mindfulness training in pregnancy. The proposed trial will determine the effectiveness of an 8-week modified Mindfulness-based Cognitive Therapy (MBCT) intervention delivered during pregnancy. Methods A randomized controlled trial (RCT) design with repeated measures will be used to evaluate the effectiveness of MBCT to treat psychological distress in pregnancy. A sample of 60 consenting pregnant women aged 18 years and above will be enrolled and randomized to the experimental (MBCT) or control (treatment as usual) condition. Primary (e.g., symptoms of stress, depression, and anxiety), secondary (cortisol, blood pressure (BP), heart rate variability (HRV), and sleep) and other outcome data (e.g., psychological diagnoses) will be collected via a combination of laboratory visits and at-home assessments from both groups at baseline (T1), immediately following the intervention (T2), and at 3 months postpartum (T3). Descriptive statistics will be used to describe sample characteristics. Data will be analyzed using an intention-to-treat approach. Hierarchical linear models will be used to test intervention effects on primary and secondary outcomes. Discussion The trial is expected to improve knowledge about evidence-based treatments for psychological distress experienced in pregnancy and to evaluate the potential impact of mindfulness-based interventions on maternal physiology.