One of the main limitations for heterologous protein production in the yeast Saccharomyces cerevisiae is the protein-folding capacity in the endoplasmic reticulum (ER). Accumulation of unfolded proteins triggers the unfolded protein response (UPR), which resolves the stress by increasing the capacity for protein folding and removal of unfolded proteins by the ER-associated degradation (ERAD) system. In order to analyze the influence of ERAD on production of a human IgG, we disrupted ERAD at different stages by deletion of the HTM1, YOS9, HRD1, HRD3, or UBC7 gene, with or without a disruption of the UPR by deletion of the IRE1 gene. All deletion strains were viable and did not exhibit a growth phenotype under normal growth conditions. Deletion of HTM1 resulted in a small increase in antibody production, whereas a small decrease in antibody production was observed in the Delta hrd1, Delta hrd3, and Delta ubc7 yeast strains, and a stronger decrease in the Delta yos9 yeast strain. Deletion of the IRE1 gene had contrasting effects in the ERAD mutants, with a strongly decreased production in wild-type cells and partially reversed effects in combination with the Delta htm1 or the Delta yos9 deletions. In order to study IgG clearance from the ER, an assay was developed using the inhibitory effect of glucose on the GAL1 promoter that is driving IgG expression. The Delta yos9 Delta ire1and Delta htm1 Delta ire1 strains showed a delayed IgG clearance from the cells, showing that removal of components for the generation and recognition of the glycan signal needed for ERAD-mediated protein degradation might increase the IgG ER residence time.