Purpose: Using COR theory to study developments of health and other key resources in self-employed workers in Sweden over 6 years, this study: (1) explored whether the heterogenous group of self-employed workers contained subgroups with different health trajectories, (2) investigated whether these were more typical for certain individuals (with respect to age, gender, sector, education, employment status), and (3) compared the different health trajectories regarding resource development in mental well-being, business resources, employment status, work ability. Method: The study used data from the Swedish longitudinal occupational survey of health (SLOSH) and included participants working as self-employed or combiner (N = 2642). Result: Five trajectories were identified with latent class growth curve model analysis (LCGM). Two health trajectories with (1) very good, respective (2) good stable health (together comprising 78.5% of the participants), (3) one with moderate stable health (14.8%), (4) one with a U-shaped form (1.9%), and (5) one with low, slightly increasing health (4.7%). The first two trajectories flourish: they maintained or increased in all key resources and were more likely to remain self-employed. Trajectories three and five consist of those who fight to maintain or increase their resources. Workers in the U-shaped health trajectory show signs of fight and flight after loss in health and other key resources. Conclusions: Studying subgroups with different resource developments over time was suitable to understand heterogeneity in self-employed workers. It also helped to identify vulnerable groups that may benefit from interventions to preserve their resources.