The younger Klitschko brother hoped for lucrative fights in the United States and thought retaining his World Boxing Organisation (WBO) crown would be merely a formality. However, his sixth defence turned into a nightmare, the 37-year-old Sanders flooring him twice in the first round of their bout on Saturday before knocking him out early in the second with a fierce left.
"He caught me by surprise," the 26-year-old Ukrainian said of a shock defeat that was met with whistles and boos from the 10,000 crowd in the Hanover hall. "Now I want a re-match. Such a thing will never happen again."
The problem is that it had already happened before, with a defeat to another boxer Klitschko was widely favoured to beat, American Ross Puritty, in 1998. The question now is whether the Germany-based Klitschko is still attractive enough for the American market.
"The defeat is a step back and a big problem for me as well," said German promoter Klaus-Peter Kohl, who represents both Vladimir Klitschko and his elder brother, Vitali. "We have to change our American plans and work hard to find an opportunity," added Kohl, who suffered another setback after Vitali saw his title fight against Britain's Lennox Lewis called off.
Vladimir Klitschko entered the fight against Sanders with a record featuring 40 wins, 37 inside the distance, and marred only by the defeat by Puritty.
"Vladimir was not cautious enough because he wanted to retaliate straight away after being floored," said Klitschko's trainer, Fritz Sdunek. "That was his main mistake. I didn't think that could happen to him again."
Klitschko, who has been dreaming for years of challenging the likes of Lewis and Mike Tyson, said he would fight to bounce back.
"Lennox Lewis came back from defeats, and so did Muhammad Ali and Max Schmeling," Klitschko said. "I'll be back."
Meanwhile Lennox Lewis may find it easier to justify his apparent decision to forego retirement following the re-ignition of his heavyweight division over the past three weeks.
On the face of it, two defeats and a mismatch involving his three most viable future opponents provides Lewis with the perfect opportunity to quit with his reputation intact, but if he plunders on in pursuit of another boost to his bulging bank balance he may find the route through the wreckage of John Ruiz and Klitschko more profitable than he could have imagined. Lewis had initially planned for three more fights involving first the elder Klitschko, Vitali, followed by the blatant financial gain of a Mike Tyson rematch and finally a showdown with Vladimir the man most observers saw as the only credible threat to his crown. But Sanders destroyed the remnants of that schedule.
That result leaves the well-and-truly vanquished Vladimir out of the picture - and also rightly or wrongly diminishes the claim of Vitali, whose credentials Lewis had already questioned.
Mike Tyson pencilled in for July called for more time after taking just 49 seconds to dismantle Clifford Etienne in Memphis. And Roy Jones' magnificent success the following week in Las Vegas ruled out the tenuous option of John Ruiz.
Ironically the biggest fight in the heavyweight division no longer involves the indisputable champion a projected Roy Jones clash with Tyson is much bigger than another Lewis-Tyson mismatch.
But if Lewis hangs around for that to happen the winner will be in a much more lucrative position to make the challenge. If Jones beat Tyson it would be no surprise to see him put a colossal weight disparity aside and target the undisputed title.