Seven years ago, Matthew O'Donnell was convicted of killing 30-year-old Noel Williamson in Caledon in October 2004.
Mr O'Donnell's lawyer's argued that the trial judge had misdirected the jury and erred by not allowing evidence of a clinical psychologist to be submitted.
The ECHR rejected the appeal and he will serve the rest of his sentence.
Mr O'Donnell, originally from County Kerry in the Republic of Ireland, is serving a life sentence at Maghaberry Prison in Northern Ireland.
In 2008, the trial judge said that Mr O'Donnell would serve at least 12 years imprisonment, a reduction from the usual starting point of 15 years, to take account of his "limited intellectual capacity".
Mr O'Donnell's IQ places him amongst the bottom 1% of the population and his understanding of spoken English is equivalent to that of a six-year-old child.
Mr Williamson, from Killylea, County Armagh, was stabbed five times in the right lower face and neck and also suffered "multiple blows of considerable force" to his head, neck and shoulders, caused by kicking or stamping.
Mr Williamson's badly beaten body was found by a man out walking his dog beside the River Blackwater.
A clinical psychologist made an assessment of Mr O'Donnell by watching videotaped interviews that Irish police conducted with him at trial.
Mr O'Donnell's lawyers argued at the ECHR that the clinical psychologist should have been allowed to share his conclusions with the court.
They also argued that no inference should have been drawn from the fact that he chose not to testify at his trial. However, the appeals were dismissed.
Mr O'Donnell was the second man to be convicted of the killing.
In 2007, 20-year-old Samuel Houston from Churchill Cottages in Caledon was jailed for eight years for the manslaughter of Mr Williamson.
The European Court of Human Rights (ECHR) has found that a man with severe learning difficulties convicted of a County Tyrone murder had a fair trial.