Euthanasia advocate Sean Davison is expected to appear in the Cape Town Magistrate's Court on Monday, facing two premeditated murder charges.
Davison, who is the founder of right-to-die organisation DignitySA, was arrested in 2013 for the death of his friend, Anrich Burger, who had become a quadriplegic after a car crash.
News24 reported that according to the charge sheet, he "administered a lethal amount of drugs to the quadriplegic deceased" at or near the Radisson Hotel in Granger Bay on November 2, 2013.
Davison, who helped his mother end her life in New Zealand, revealed to News24 in 2014 that he had helped Burger to do the same.
The second charge is in connection with the death of Justin Varian in 2015. Varian was suffering from motor neuron disease.
The State accuses Davison of "placing a bag over the deceased head and administering helium with the intent of helium deoxygenation and/or asphyxiation".
During his first court appearance, through an affidavit read out by his lawyer, Davison maintained that he was not guilty of any crime.
"It is and has always been my contention that I have not committed any offence as alleged in this matter," his lawyer Joshua Greeff read.
Earlier this year, News24 reported that Davison was trying to raise around R2.8m to pay for his legal costs.
At the time of publication in February, a trust account with his attorneys had already received around R400 000 in donations.