Abstract This paper presents an analysis of total costs (TPC) and energy efficiency of enzymatic ethanol production. The analysis is parametrized with respect to plant capacity and polysaccharides content (pc) of lignocellulosic feedstock. The feedstock is based on wheat straw whose price is proportional to its pc ranging from new straw with high pc and high cost to agro-wastes with limited pc but lower cost. The plant flowsheet was built using a conventional biochemical platform with co-saccharification and fermentation (SHF) technologies. A parametric analysis of TPC as a function of plant capacity (100–2100ton DB/day) and pc (i.e. feedstock price) (80% (75 USD/ton DB)–35% (6 USD/ton DB)) was performed with Net Present Value (NPV) techniques. Current data from Mexican economics and the agro-industrial sector were used as an illustrative case. A quasi-linear section of the TCP surface was identified delimited by (300–1100ton DB/day) and (80–55% pc) with increments no larger than 21% of the minimum TPC obtained (0.99 USD/l etOH for 2100ton DB/day and 80% pc). Major cost contributions are detailed and quantified for boundary cases of this surface. Energy consumption and production were also calculated for all the plant capacity and feedstock pc cases, taking into consideration the Maximum Energy Recovery (MER) obtained from a Pinch analysis. The end-use energy index eer was less than 0.82 for all cases, thus stressing the need to use process equipment with lower energy requirements. TPC are compared against previously published results for SHF technology between 500 and 2100ton DB/day plant capacities. These values were updated and normalized with respect to feedstock and enzyme costs employed in this work. Differences among TPC and recently published normalized results are within a ±5% range, thus confirming the dependence of TPC from feedstock and enzyme prices, regardless of flowsheet technology and economic conditions.