Just like the death of Walt Disney changed Disney forever, Enderle said, the permanent absence of Jobs would turn Apple into a company that's much more like the typical technology company. It may take years for the erosion to hit but, he said, over time it will be clear that without Jobs, the company will never be the same again.
"More products, a lower hit rate," he said. "That's the standard way of doing things because most companies don't have Steve Jobs."
Tim Bajarin, Silicon Valley analyst and president of Creative Strategies, said that in the near-term, Apple investors should have little to worry about.
"Tim Cook and Apple's executive team already showed that they can keep Apple humming in Steve's absence. I really don't think there will be any change," he said.
Any products due out in the next one to two years already have Jobs' approval, he said.
"Here's a guy who has lived and breathed Apple for the past 10 years. He understands Steve's thinking. He understands Steve's vision and I have no doubt that Apple would be fine for the next 2 to 5 years," he said.
Since Jobs' return to work in June 2009, he has unveiled the iPhone 4, the newest MacBook air and his revolutionary iPad.
Jobs has not been seen at an Apple event since October 2010. When Verizon announced this month that it would carry Apple's iPhone, it was Cook – not Jobs – who represented Apple at the New York event.
During his 2009 absence, analysts said Apple and Cook did just fine, partly because Jobs was available for big decisions, partly because he has delegated day-to-day decisions for about five years.
In his e-mail today, Jobs said he has "great confidence" that Cook and the rest of the management team will do a "terrific job" in his absence.
"I love Apple so much and hope to be back as soon as I can. In the meantime, my family and I would deeply appreciate respect for our privacy," Jobs said in his company e-mail.
ABC News' Dan Arnall contributed to this report.