Background: Shift work is considered a risk factor for a number of chronic health conditions including obesity. Weight reduction in obese patients lowers the risk for cardiovascular disease, diabetes, certain cancers, and mortality. Achieving a negative energy balance by providing low-calorie meal replacements is widely used for weight management. This study aims to evaluate the impact of a low calorie “meal-replacement” on weight and metabolic parameters of shift workers with obesity. Methods: This trial will be conducted in parallel, randomized controlled design for a period of 8 weeks. A total of 44 shift workers with Body Mass Index over 25 kg/m2 will be recruited after assessing eligibility. Participants will be randomly assigned to the test and control groups on a 1:1 ratio. The intervention group (N=22) will be provided with a low calorie (~200 kcal) meal replacement shake as a dinner, and the control group (N=22) will continue their habitual diets. The visits and the evaluations will be done as follows: screening (visit 0), 4 weeks (visit 1), and 8 weeks (visit 2). Anthropometric measurements will be taken at 0, 4 and 8 weeks. Body composition, biochemical parameters, dietary intake and physical activity will be assessed during the first and the last visit. Outcomes: The primary outcome will be body weight loss, and the proportion of participants that had a 5% body weight loss from baseline. The secondary outcomes will be post intervention changes in the other metabolic parameters. Discussion: To our knowledge this is one of the first randomized controlled trials evaluating the effects of a meal replacement as the night meal for weight loss in shift worker with obesity. Moreover, improvement of metabolic parameters in shift-workers will be an added benefit to this high risk group. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622000231741. Registered on 09 February 2022. https://www.anzctr.org.au/ACTRN12622000231741.aspx