Up to 250 jobs have been axed as both a global healthcare firm and brewer culled staff numbers.
Multinational Baxter Healthcare revealed it would lay off 150 workers over the coming year in Castlebar, Co Mayo, while a further 50 temporary contracts would not be renewed.
Elsewhere, cider maker Bulmers announced plans to axe 50 workers from a manufacturing plant in Clonmel, Co Tipperary, by Christmas.
Politicians described the cuts as a shattering blow to the rural towns.
Baxters claim the drop in the workforce is driven by the global economic downturn, the subsequent impact of European healthcare cost-savings measures and the ongoing need to improve our cost competitiveness.
Pat Gallagher, general manager, said the decision was a necessary step to secure the long-term viability of the operation, which had a 1,100 strong workforce."
Fine Gael's John O'Mahony said his thoughts went out to the workers in Baxter Pharmaceuticals and their families.
"At a stroke of a pen, the effect of the jobs announcement two weeks ago has been wiped out," he said. "Baxter has been a wonderful employer for 30 years and the loss of these jobs will be keenly felt everywhere in Mayo."
Meanwhile, management at the Bulmers facility in Co Tipperary blamed the fall in sales of cider in pubs and the rise in consumers heading to off-licences on the decision. Its cost reduction and reorganisation programme, which the company claims will secure 220 remaining jobs, is expected to be complete by December.
Bulmers general manager Paul O'Sullivan said: "It is with regret that we have to commence this programme of job cuts. The combined impact of a dramatically weakening consumer environment and the continued migration of cider volumes from the on to off trade channel has adversely impacted our business in Ireland."