The paper proposes an empirical investigation on the identification and analysis of the most relevant barriers to energy efficiency within 48 manufacturing Italian Small and Medium-sized Enterprises (SMEs). The barriers have been analyzed following an innovative taxonomy that has been adapted to empirical research and is able to highlight the differences between perceived and real barriers, the effect of the barriers on decision-making processes, and interactions among found barriers. Indeed, the results provide a relevant contribution for a full comprehension of those issues, which is crucial for developing the most suitable means for the promotion of energy efficiency. Firstly, the perceived barriers emerged in the study belong to economic and information areas, with a minor contribution of behavioral barriers. This perception is not confirmed by analyzing the real barriers: indeed, the most relevant are the lack of interest in energy efficiency and the existence of other priorities, that, by the fact, seem to downgrade energy efficiency to a marginal aspect of the operations by decision-makers. Secondly, by looking at the effect of the barriers on the decision-making process, the perceived difficulties do not take place exclusively in the analysis of the investment to be undertaken and the intervention implementation, but, with comparable importance, also in the generation of interest and knowledge of the opportunities. Thirdly, the analysis of the sample seems to highlight the existence of other factors affecting barriers to energy efficiency, e.g. firm’s size and energy expenditures. This empirical investigation has pointed out that, when analyzing barriers to energy efficiency, it seems not fully appropriate to bundle together SMEs, since relevant differences can be appreciated both for perceived and real barriers. This is quite important for future energy policies, since, at the moment, SMEs are usually considered by policy-makers as a whole.