The Archbishop of York said he plans to write to firms in the city who have together announced more than 1,600 job cuts in the last year.
Dr John Sentamu said he wanted to see firms invest more in the city
Dr John Sentamu said he will appeal to executives to face up to the human cost of unemployment.
His comments come after Nestle revealed plans to axe 645 jobs. The firm previously cut 234 jobs in the city.
In the past year York has also suffered job cuts by Aviva, which owns Norwich Union, Terry's and British Sugar.
Dr Sentamu said: "My hope is that these companies realise that for each single job loss they announce, there is a family or an individual facing the potential misery of financial insecurity.
"Inward investment in the region is always welcome, and assurances of increased levels of investment are signs of hope.
"However for those skilled, manufacturing workers there are not always newly created skilled manufacturing jobs to be found."
Dr Sentamu said he wanted to express his concerns for the firms' continuing workforces and his wish for greater levels of future investment.
He said he hoped "the full human cost of these job losses remains at the forefront of any further decisions with regard to these industries in York".
Meanwhile, City of York Council has set up a redundancy support group to help those affected by recent job loss announcements.
The council will work with regional development agency Yorkshire Forward, JobCentre Plus, York College and other agencies to offer advice or to help to anyone who might need to learn new skills or gain qualifications in order to get back into employment.