Abstract In this paper, performance of some zeotropic mixtures has been estimated and compared with pure fluids for the use in two options of mini solar Combined Heat and Power (CHP) units based on Organic Rankine Cycle (ORC). Optimization potential and comparison of such mini systems have been mainly aimed and assessed within this analysis for predefined energy outputs. To achieve these goals, energetic and economic criteria have been identified with help of numerical simulations. The results showed that compared to pure R134a and R245fa, the mixture R409A is strongly recommendable when gaining the heat demand over ORC condenser (common ORC-CHP method), where it could reduce the production cost of the energy unit till 16.20%. For the series ORC-CHP layout, R401A becomes the relevant candidate from economic point of view, where a promotion of 4.49% could be registered with this mixture. Moreover, R401B also exhibits attractive performances in the both systems. Furthermore, comparing the two exploitation concepts demonstrated that the series one is more feasible than the common one within scope of this study. Finally, using R401A in the series unit could lead to combined optimization ranging between 16.5% and 47% versus R134a in the common method.