Background <p>Treatment for symptoms associated with environmental factors (SAEF), such as electrohypersensitivity or multiple chemical sensitivity, have been sparsely investigated thus far.</p> Methods <p>In this parallel, two-armed open-label randomized controlled trial, we will apply a treatment model for SAEF based on cognitive behavioral therapy. Our goal is to recruit <i>N</i> = 68 people with either multiple chemical sensitivity or electrohypersensitivity, or both, by informing our professional network of healthcare practitioners and patient groups. Prospective participants will be randomized into a treatment or a waitlist-control group. The primary outcome is physical health-related quality of life, while attendance, measures of symptom experience, cognitive and emotional processing, and comorbid psychopathology will be assessed as secondary outcomes. Delivered in-person and/or online through videoconferencing tools, the treatment will consist of 12 individual CBT-inspired sessions, guided by specialized psychologists and spanning eight weeks. Patients will be assessed at three timepoints, each 3 months apart, meaning we will have pre- and post-treatment measurements for both groups.</p> Discussion <p>This randomized controlled trial will be the first to thoroughly test a cognitive behavioral therapy intervention for individuals living with SAEF. We intend to meet critical unmet needs for specialized healthcare in this population. Additionally, by adding many secondary outcomes that have not, or not sufficiently, been studied in individuals with SAEF, we will gain a more comprehensive understanding of these patients’ thoughts, feelings, and behaviors.</p> Trial registration <p>This trial was first prospectively registered at ClinicalTrials.gov, code NCT05973214, on the 26th July 2023.</p>