This paper proposes a model for managing a packaging process of small products at a production line. The aim of the paper is to determine the optimal size of a box the products are stored in considering both financial (in terms of cost) and ergonomic (in terms of worker fatigue) aspects. The paper first develops a biomechanical model to estimate the expected fatigue-recovery parameters associated with the packaging process. Secondly, it proposes an optimization model that minimizes the total relevant cost of the packaging process consisting of the cost of packaging material and the cost of working time, which includes the time required for packing items, setting up and handling boxes, transporting boxes to the shipping area, and idle time cost. Thirdly, the fatigue-recovery approach is integrated into the optimization model to determine the optimal box size from a given set of alternative boxes as well as the work schedule that minimize the total relevant cost while satisfying the upper bound on the estimated total (accumulated) fatigue level. The developed model is then analysed in a numerical experiment inspired by a case observed in industry. The results of the numerical analysis show that smaller box sizes are less sensitive to changes in the maximum permitted fatigue level and that they lead to lower total relevant cost for low wage cost. Larger boxes, in turn, are recommended for higher wage cost. The maximum permitted fatigue level and the box sizes also influence the fatigue range experienced by the worker as well as the share of productive time the worker spends on the job.