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Stress is accepted as a contributing factor to the onset of a range of adverse mental health disorders, including depression and anxiety. There is an urgent need for effective digital mental health interventions to address the adverse outcomes of stress-related disorders. Few studies have directly demonstrated the efficacy of app-based mindfulness interventions in populations with elevated stress levels. The current study examined if app-based guided mindfulness could improve subjective levels of stress and influence physiological markers of stress reactivity in a population with elevated symptoms of stress. The study included 163 participants who had moderate to high perceived stress (PSS-10, Perceived Stress Scale: 14-40). Participants were randomly allocated to 1 of 5 groups: a digital guided program designed to alleviate stress (Managing Stress), a digital mindfulness fundamentals course (Basics), digitally delivered breathing exercises, an active control intervention (audiobook), and a waitlist control group. The three formats of mindfulness interventions (Managing Stress, Basics, breathing) all had a total duration of 300 minutes spanning 20-30-days. Primary outcome measures were perceived stress using the PSS, self-reported sleep quality using the PSQI (Pittsburgh Sleep Quality Index), and trait mindfulness using the MAAS (Mindful Attention Awareness Scale). To probe the effects of physiological stress, an acute stress manipulation task was included, specifically the cold pressor task (CPT). Heart rate variability (HRV) was collected before, during and after exposure to the CPT and used as a measure of physiological stress. The results showed that PSS and PSQI scores for the Managing Stress and Basics groups were significantly reduced from pre to post while no significant differences were reported for the other groups. The physiological results revealed that the Managing Stress and Basics groups displayed reduced physiological stress reactivity from pre to post before, during, and after the CPT. There were no significant differences reported for the other groups. Subgroup analyses stratified participants in the Basics and the Managing Stress by baseline stress levels using the median PSS score into either moderate or high stress. Only the Managing Stress subgroup showed improved PSS scores among high stress participants, while there was no significant difference in PSS reduction by subgroup for the Basics group. These results demonstrate efficacy of app-based mindfulness in a population with moderate to high stress on improving self-reported stress, sleep quality and physiological measures of stress during an acute stress manipulation task.