The pair were acquitted of the November 2007 murder in Perugia in March this year, bringing an end to a sensational eight-year legal drama.
In reasoning made public on Monday and reported by Ansa, the Court of Cassation said that there was an “absolute lack of biological traces related to them" in the room where the murder took place and on the victim's body.
Kercher, 21, died after being stabbed 47 times and having her throat slashed. Her half-naked body was found in a pool of blood in a back room of the house she shared with Knox on via della Pergola in the Umbrian city.
The court said that the case lacked a "probative totality" marked by "evidence beyond reasonable doubt".
The verdict from Italy’s top appeals court marked the end of a legal battle which included both Sollecito and Knox spending four years in prison before a guilty verdict was overturned once before in 2011.
But they were convicted for a second time in 2014 by a Florence appeals court. That verdict was overturned in late March.
Ivory Coast-born Rudy Guede was jailed for the murder in 2008 but, in a judgement that was to have serious implications for Knox and Sollecito, the judge in his trial ruled that he could not have acted alone.