Public Health England is looking into a spate of drug deaths, including seven in Barnsley.
It is believed that heroin contaminated with powerful painkillers, fentanyl and carfentanyl, could be responsible or the deaths in April.
A number of other deaths across Yorkshire and now further afield are now being looked at for possible links.
Rosanna O’Connor, Director of Drugs, Alcohol and Tobacco for Public Health England said: "There have been a number of recent deaths involving fentanyl, primarily in Yorkshire and the Humber and cases are now emerging in other parts of the country, which we are investigating.
“Fentanyl and, in particular carfentanyl, are so strong that small amounts can cause overdose.
"In April we issued a national drugs alert to warn medical and emergency and drugs services of the need to be vigilant.
“We are using our networks to lead further investigations, working closely with coroners, the police, drug testing labs and local drug services to get more information on confirmed and suspected cases.
“Plans are also in place for a scaled-up response pending our investigations. This includes ensuring sufficient stocks of naloxone to treat overdoses.”
She urged heroin users to be on their guard.
“We are urging heroin users to be extra careful. We strongly advise them not to use alone and to test a small amount first," she added.
"They need to look out for each other and be alert to any signs of an overdose, such as lack of consciousness, shallow or no breathing, snoring, and blueing of the lips and fingertips.
"If possible, they should use naloxone if someone overdoses, and immediately call for an ambulance. We strongly advise all dependent drug users to get support from local drug services.”
Fentanyl is an anaesthesia used to help prevent pain after surgery or other medical procedures and is 100 times more potent than street heroin.
Carfentanyl is stronger than Fentanyl and is used on animals.
Anyone with information about drug dealers in South Yorkshire should call South Yorkshire Police on 101 or Crimestoppers, anonymously, on 0800 555111.