Psychological stress exacerbates many pathological conditions including inflammatory skin conditions. The effect of psychological stress on acute radiation-induced skin reactions has not been documented before. Here, we aimed to explore if psychological stress could aggravate skin reaction severity in breast cancer patients. We conducted a secondary analysis of patient data obtained during a randomised, controlled clinical trial for acute radiation-induced skin reaction severity in 78 breast cancer patients. Patients were assessed three times a week during treatment. Skin reaction severity was measured using the modified Radiation-Induced Skin Reaction Assessment Scale (RISRAS) and Radiation Therapy Oncology Group grades. Stress levels were determined using a 5-point LIKERT scale to rate physical well-being, managing stress levels, house, family, work and other commitments. A total of 20 patients (26%) of the 78-patient cohort were considered stressed. Skin reaction severity in stressed patients was twice that of non-stressed patients (p < 0.001) and stressed patients were five times more likely to develop moist desquamation. Our results show that psychological stress aggravates skin reaction severity during radiation therapy. This research needs to be validated in a more rigorous manner by incorporating a validated scale such as the Distress Thermometer and Impact Thermometer in future skin trials.