Leishmania causes cutaneous and visceral diseases affecting millions of patients worldwide. The parasite cycles between two different hosts, insect and mammalian. In this study, we determined the landscape of 2’-O- methylation (Nm) modification on Leishmania rRNA, and found two Nm positions that are differentially modified during cycling between the two life stages. Cryo-EM structures of ribosomes from cells overexpressing a guiding snoRNA compared to an inactive mutant at ~2.3-2.7 Å resolution did not reveal structural changes in the small subunit rRNA carrying the specific Nm modification. However, changes were observed in H68 of the large subunit rRNA due to a second base-pairing interaction, thus reviving the concept of chaperone activity for snoRNAs. Based on our high-resolution structure, translatome and tRNA analysis, we propose a mechanism whereby changes in the ribosome structure affected the release of specific tRNAs, which are correlated with changes in translation of only a subset of mRNAs.