Parasitic helminths use two benzoquinones as electron carriers in the electron transport chain. In normoxia they use ubiquinone (UQ), but in the anaerobic conditions inside the host, they require rhodoquinone (RQ) and greatly increase RQ levels. We previously showed the switch from UQ to RQ synthesis is driven by a change in substrates by the polyprenyltransferase COQ-2 (Del Borrello et al., 2019; Roberts Buceta et al., 2019) - how this substrate choice is made is unknown. Here, we show helminths make two <i>
coq-2</i> splice forms, <i>
coq-2a</i> and <i>
coq-2e</i>, and the <i>
coq-2e-</i>specific exon is only found in species that make RQ. We show that in <i>C. elegans</i> COQ-2e is required for efficient RQ synthesis and for survival in cyanide. Crucially, parasites switch from COQ-2a to COQ-2e as they transition into anaerobic environments. We conclude helminths switch from UQ to RQ synthesis principally via changes in the alternative splicing of <i>
coq-2.</i>