Harper was asked about outmigration and what, if any, relationship it may have to EI changes while he was in Prince Edward Island, a province where those changes have been met with protest.
"To the extent that there's outmigration, it has nothing to do with the employment insurance system," Harper said after a funding announcement in Charlottetown.
"It is just the reality and it's not unique to Prince Edward Island that there are greater economic opportunities, particularly for young people, more economic opportunities in some parts of the country than others."
Premier Robert Ghiz has called on the federal government to reverse the changes, saying he is concerned they will hurt his province's businesses and seasonal industries.
Harper said the federal government has been monitoring the changes and a "minuscule" number of people have been disqualified from receiving EI since the changes were implemented in January 2013.
"These are obviously cases where people are simply not eligible," he said.
Under the changes, those who frequently claim EI need to prove they're actively seeking work. People must also accept a job within 100 kilometres of their home as long as they are qualified and the pay is at least 70 per cent of their previous salary.
The changes to the EI program have prompted numerous protests across Atlantic Canada.
The federal government has said the changes will better connect people with available job opportunities and they were required as a result of unprecedented labour and skills shortages.
The changes to the program are expected to save the public treasury $33 million this year.