Entrepreneurs engaged in start-up activity are confronted with a particularly high degree of diverse demands. At the same time, their efforts to deal with those demands are not immediately rewarded in terms of money, esteem and status control, potentially resulting in effort-reward imbalance (ERI) which in turn can lead to stress reactions. However, we do not know how the characteristics of the entrepreneurial life cycle influence the development of stress reactions, which might explain the heterogeneity of empirical research on entrepreneurial stress. By exploring early-stage entrepreneurs’ work-related efforts, rewards and their stress reactions as a result of ERI in conjunction with coping strategies, we aim to extend and nuance the Effort-Reward Imbalance model (Siegrist, 1996) specifically for the entrepreneurship context.