The success of the campaign to try to save the Burberry factory in Rhondda could put off future companies investing in Wales, it is claimed.
More than 300 people will lose their job when the plant closes
CBI Wales director David Rosser said flexibility was one of the main factors for firms looking to invest here.
Burberry has now offered a loyalty bonus to the 300 staff at Treorchy along with a £1.5m local trust fund.
AM Leighton Andrews, one of those fighting for the factory, said Mr Rosser's comments were "ill-judged".
The plant, which makes polo shirts for the designer label, is due to close at the end of March, although the company says about a third of workers have already found jobs.
On Friday campaigners said they had won "significant improvements" on previous offers from Burberry with a multi-million pound boost to the redundancy package.
But they insisted their high-profile anti-closure campaign which has attracted the support of a host of celebrities over the last six months would go on.
Mr Rosser told BBC Radio Wales international companies were watching what was happening with Burberry "very closely".
"I've had some messages though largely from concerned Welsh people living and working in the city of London living and working in the business community who are a little worried," he said.
"Wales as a business location looks a little less friendly, a little less attractive than it used to.
Mr Rosser said if he was "running the Welsh Assembly Government's inward investment operation now I'd think my job has become a little harder".
Celebrities have backed the Burberry campaign
"Because whether we like it or not flexibility for businesses is far more important than it used to be.
"Companies now have to react and change, they have to restructure sadly more often than they had to. If they don't, frankly, they die."
Asked whether the politicians who have put their name to the Burberry campaign were damaging the Welsh economy, Mr Rosser said: "I think we've got to that stage with this particular campaign, yes.
He said Burberry was a well-connected company and members of the business community have said: "Are we going to go through that if we end up in Wales?"
But Rhondda AM Mr Andrews said Mr Rosser's comments were ill-conceived.
Ignorant and ill-judged
"The reality throughout the campaign has been that the high-profile nature of it has attracted business interest both within Wales and outside Wales," Mr Andrews said.
"I've had companies from England getting in touch about the skills of the Burberry workers because those kind of skills are needed.
"I think what was said by the director of CBI Wales was frankly ignorant and ill-judged."
Burberry announced in September that it would close the Rhondda factory, transferring production of its designer label polo shirts overseas.
But workers and unions immediately launched their campaign, accusing the firm of abandoning its British roots.
Co-ordinated protests were staged in London, Paris, New York, Chicago, Strasbourg and Las Vegas earlier in February.
Later this month a concert is to take place at Ystrad Leisure Centre in Rhondda featuring The Automatic, Goldie Lookin' Chain, and The Alarm.