This data article contains data related to the article ". Comparison of codon usage bias across Leishmania and Trypanosomatids to understand mRNA secondary structure, relative protein abundance and pathway functions" by Subramanian and Sarkar, Genomics, 2015 (. 10.1016/j.ygeno.2015.05.009). The data comprises of sequence-based measures that quantify the effect of codon usage across genomes. The data thus generated represents computed values of codon usage indices like relative synonymous codon usage (RSCU), effective number of codons (ENC), and codon adaptation index (CAI), a set of single copy orthologous genes common to the 13 Trypanosomatids, and comparisons of CAI between genes of different functions. This forms a basis of comparison to infer the causes and consequences of codon usage bias in Leishmania and other Trypanosomatids. © 2015 Elsevier Inc.