Genome-wide patterns of codon bias are shaped by natural selection in the purple sea urchin, Strongylocentrotus purpuratus.  Codon usage bias has been documented in a wide diversity of species, but the relative contributions of mutational bias and various forms of natural selection remain unclear. Here, we describe for the first time genome-wide patterns of codon bias at 4623 genes in the purple sea urchin, Strongylocentrotus purpuratus. Preferred codons were identified at 18 amino acids that exclusively used G or C at third positions, which contrasted with the strong AT bias of the genome (overall GC content is 36.9%). The GC content of third positions and coding regions exhibited significant correlations with the magnitude of codon bias. In contrast, the GC content of introns and flanking regions was indistinguishable from the genome-wide background, which suggested a limited contribution of mutational bias to synonymous codon usage. Five distinct clusters of genes were identified that had significantly different synonymous codon usage patterns. A significant correlation was observed between codon bias and mRNA expression supporting translational selection, but this relationship was driven by only one highly biased cluster that represented only 8.6% of all genes. In all five clusters preferred codons were evolutionarily conserved to a similar degree despite differences in their synonymous codon usage distributions and magnitude of codon bias. The third positions of preferred codons in two codon usage groups also paired significantly more often in stems than in loops of mRNA secondary structure predictions, which suggested that codon bias might also affect mRNA stability. Our results suggest that mutational bias has played a minor role in determining codon bias in S. purpuratus and that preferred codon usage may be heterogeneous across different genes and subject to different forms of natural selection.