Abstract Potential energy feedstocks from conventional agriculture usually include pure vegetable oil (PVO) and agricultural/forest residues. Their uses can represent a starting point for the development of short agro-energy chains in the south areas of the Mediterranean region. This paper focused on testing and awareness raising of biofuel production for the cogeneration of electricity and heat from PVO of two Brassica oilseed crops in Sicily (Italy). The main aims of this study were: i) to evaluate the agronomic performance of rapeseed (Brassica napus L. var. oleifera D.C.) and Ethiopian mustard (Brassica carinata A. Braun) in semi-arid climate condition; ii) to analyze the quality of PVO and the chemical-physical characteristics of pure vegetable oils, defatted seed meals and crop residues of the two species; iii) to define the economic viability of a pilot combined heat and power (CHP) plant operating on PVO. In this study, seed and crop residue yields were determined at the harvesting stage on a harvest area of 10 m2. For each species, chemical-physical characterizations were carried out using specific protocols. The cogeneration of heat and electricity was carried out using a CHP system with a nominal power of 75 kWh. The final stage of the study focused on the economic viability analysis of the CHP system. Seed yields of rapeseed and Ethiopian mustard were 2.10 and 1.16 t ha−1 on average, respectively. Ethiopian mustard obtained the highest performance of aboveground biomass yield (5.31 t ha−1). The fatty acid profiles of the PVO resulted different for the two oilseed crops. Ethiopian mustard had, on average, the highest glucosinolate content in the seeds. The cogenerator showed a consumption of 14.4 kg PVO h−1 on average. Cash-flow trend analysis showed good economic benefit for farmers. These results make the two species as promising energy crops for suitable short agro-energy chains in the south Mediterranean areas.