Bristol toddler Jayden-Lee Green had methadone in body
His parents Jamie Green, 32, and Sonia Britton, 35, are charged with manslaughter and causing and allowing the death of a child.
Mr Green, who appeared at Bristol Crown Court via video link on Friday, is also charged with wilful assault.
The prosecution said tests showed the cause of death was connected to the high concentration of the heroin substitute methadone found in Jaden-Lee's body.
Mr Green and Ms Britton were remanded in custody to appear at Bristol Crown Court on 16 December.
Avon and Somerset Police are appealing for anyone with information to contact the force.