BACKGROUND: Reduced Environmental Stimulation Therapy (REST) is a behavioral intervention that systematically attenuates external sensory input to the nervous system. Previous studies have demonstrated acute anxiolytic and antidepressant effects of single sessions of REST in anxious individuals, however the duration and time course of these effects is unknown. In the current study, we used experience sampling and multiple sessions of REST to explore the time course of the anxiolytic and antidepressant effects over a 48-hour time period. METHODS: 75 adults with anxiety and/or depression were randomized to complete 6 sessions of REST (either pool-REST, pool-REST preferred, or chair-REST). Post-REST effects were tracked using experience sampling on a smartphone with a ten-item survey administered at 6 time points for each session (i.e., immediately before and after REST and then 4, 8, 24, and 48 hours later). Using principal component analysis, responses to survey items at baseline were reduced to broad symptom clusters of anxiety, depression, and serenity and were utilized in linear mixed effects models to determine the magnitude and time course of post-REST effects. RESULTS: REST was associated with significant decreases in anxiety and depression, and significant increases in serenity, with effects lasting for 48 hours. Repeated exposure to REST was associated with lower baseline levels of anxiety at later sessions. CONCLUSION: These initial findings suggest that the anxiolytic and antidepressant effects of REST persist for at least two days, and that repeated REST sessions may have additive effects on lowering anxiety-related symptoms. These findings could help to determine the optimal intervention frequency of REST and facilitate future investigations focused on the combination of REST with standard treatments for anxiety and depression.