Thecosome pteropods, a group of calcifying holoplanktonic mollusks, have recently become a research focus due to their potential sensitivity to increased levels of anthropogenic dissolved CO₂ in seawater and the accompanying ocean acidification. Some populations, however, already experience high CO₂ in their natural distribution during diel vertical migrations. To achieve a better understanding of the mechanisms of pteropod calcification and physiological response to this sort of short duration CO₂ exposure, we characterized the gene complement of Clio pyramidata, a cosmopolitan diel migratory thecosome, and investigated its transcriptomic response to experimentally manipulated CO₂ conditions. Individuals were sampled from the Northwest Atlantic in the fall of 2011 and exposed to ambient conditions (~ 380 ppm) and elevated CO₂ (~ 800 ppm, similar to levels experienced during a diel vertical migration) for ~ 10 h. Following this exposure the respiration rate of the individuals was measured. We then performed RNA-seq analysis, assembled the C. pyramidata transcriptome de novo, annotated the genes, and assessed the differential gene expression patterns in response to exposure to elevated CO₂. Within the transcriptome, we identified homologs of genes with known roles in biomineralization in other mollusks, including perlucin, calmodulin, dermatopontin, calponin, and chitin synthases. Respiration rate was not affected by short-term exposure to CO₂. Gene expression varied greatly among individuals, and comparison between treatments indicated that C. pyramidata down-regulated a small number of genes associated with aerobic metabolism and up-regulated genes that may be associated with biomineralization, particularly collagens and C-type lectins. These results provide initial insight into the effects of short term CO₂ exposure on these important planktonic open-ocean calcifiers, pairing respiration rate and the gene expression level of response, and reveal candidate genes for future ecophysiological, biomaterial and phylogenetic studies.