Foreign Minister Micheline Calmy-Rey says the Swiss policy of conducting bilateral negotiations with the European Union is becoming increasingly difficult.
She told a conference organised by Geneva University's European Institute that the issue had reached a turning point.
She said the 27 EU members were "beginning to have had enough" of special demands from Bern.
"They are getting fed up with Switzerland which asks all the time for specific solutions on every issue. That's a big burden for them and it's not easy for Switzerland, with 27 states facing it," she said.
"The bilateral relations path is not one that's strewn with rose petals. It's becoming increasingly complex and we run the risk of losing ourselves in details and not seeing the whole picture.
"We are still able to defend our interests but things are changing rapidly," she added.
Switzerland has concluded more than 20 bilateral accords with Brussels, but voters in 1992 rejected the European Economic Area treaty – a halfway house to EU membership.
swissinfo.ch and agencies