We study a multi-skilled worker assignment problem with multiple shifts in cell manufacturing. The problem is motivated by a real planning problem in protective device manufacturing. Two assignment decisions must be made simultaneously: Requested orders and multi-skilled workers are assigned to production cells and shifts. Specifically, a certain number of workers process orders in one production cell, whereby the processing times of the orders vary depending on this number of assigned workers. We also take into account family setup times, invalid worker-cell combinations, and a limited number of possible shifts for each order to process. A 0–1 integer linear programming model that minimizes the total number of cells opened for production in all shifts is introduced. The model is tested using real-world data. We show that the generated solutions are suitable to support production planners and can be used to reveal problems of the production such as lack of workers and skills or disruption-prone cells with a high utilization.