Road accident victim Paul Lamb and the family of the late locked-in syndrome sufferer Tony Nicklinson have lost a right-to-die challenge at the Court of Appeal.
Judges rejected their appeal against the long-established legal position that voluntary euthanasia is murder.
Former builder and father-of-two Mr Lamb, 57, from Leeds, who wants a doctor to help him die in a dignified way, had won the right to join the litigation to continue the battle started by Mr Nicklinson.
Mr Nicklinson, 58, died at home in Melksham, Wiltshire, in August 2012, a week after he lost a High Court bid to end his life with a doctor's help.
The father-of-two, who was paralysed by a stroke while on a business trip to Athens in 2005, had refused food and contracted pneumonia after he was "devastated" by the decision.
During the appeal hearing the judges heard argument that people who are too sick or disabled to end their "unbearable" lives without help are currently being condemned to "suffer in silence or make desperate attempts to kill themselves".
The ruling was given by the Lord Chief Justice Lord Judge, Master of the Rolls Lord Dyson and Lord Justice Elias.
Mr Lamb said he was "absolutely gutted" by the decision.
He added: "I was hoping for a humane and dignified end. This judgment does not give me that.
Paul Lamb said he was "absolutely gutted" by the judgment "I will carry on the legal fight - this is not just about me but about many, many other people who are being denied the right to die a humane and dignified death just because the law is too scared to grapple with these issues."
Via Twitter, the Nicklinson family said: "We are sorry to say that we have lost our Court of Appeal challenge."
They said they "will continue the legal campaign and appeal again".
The Court of Appeal granted the family permission to appeal to the Supreme Court, the UK's highest court.
Lawyers for a third man welcomed a ruling in his case asking for clearer guidance from the Director of Public Prosecutions (DPP) for carers or health professionals assisting those wishing to end their own lives.
Martin, 48, who cannot be identified for legal reasons, needs the assistance of a doctor, nurse or carer to help him die because his wife does not want to be actively involved in bringing about his death.
His lawyers say that current DPP guidance makes clear that friends or family members are unlikely to be prosecuted, but does not cover health professionals.
Speaking by means of special computer software, Martin said in response to the judgment: "I am delighted by the judgment today. It takes me one step closer to being able to decide how and when I end my life.
"I am only unable to take my own life because of my physical disabilities. Almost every aspect of my daily life is outside of my control.
"I want, at least, to be able to control my death and this judgment goes some way to allow me to do this."
The Crown Prosecution Service (CPS) said it has made an application to the Court of Appeal for permission to appeal to the Supreme Court over the issue.
DPP Keir Starmer said: "While I respect the carefully considered judgment of the Court of Appeal, I think it would be sensible for the CPS, if possible, to have the benefit of the views of the Supreme Court before any amendments are made to the DPP's guidelines in this important and sensitive area of the law."
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