The highly conserved nonsense-mediated mRNA decay (NMD) pathway was initially identified as an mRNA surveillance pathway. NMD is now also known to have multiple functions including precise regulation of gene expression. In Saccharomyces cerevisiae, about 5-10 % of the transcriptome is regulated by the NMD pathway. Previous studies found environmental condition-specific regulation of transcripts by NMD in S. cerevisiae. In this study, we examined the effect varying copper levels have on global regulation of mRNAs by NMD. Specifically, the consequences of copper excess and deficiency on cellular ultrastructure and transcriptomes of S. cerevisiae cells with a functional and non-functional NMD pathway was investigated. Copper excess or deficiency resulted in enlarged vacuoles in yeast cells relative to cells grown in normal growth conditions. Additionally, yeast cells with a functional NMD pathway had dilated endoplasmic reticulum (ER) when exposed to elevated copper levels. In elevated copper levels dilated ER were not observed in cells with a non-functional NMD pathway. Furthermore, copper deficiency led to widespread changes in gene expression relative to the normal growth and elevated copper conditions. Significant enrichments for Molecular function (MF) included transmembrane transporter activity and helicase activity for transcripts upregulated in complete minimal (CM) only. For transcripts upregulated in both CM and 100 μM copper, significant enrichments for MF were found in structural constituent of cell wall, ferric-chelate reductase (NADPH) activity, metal ion and DNA binding. Transcripts upregulated specifically in low copper were greatly enriched for categories related to RNA binding and RNA metabolic processes.