Emergency services were called to the Bullring at about 12.24am on Friday morning to a report a woman had been found unconscious in the street.
The woman, who was 35, was taken to hospital but later died.
A postmortem will be conducted to determine a cause of death.
A 51-year-old male was taken to hospital with her for treatment.
Detective Inspector Jordan Piper of Wakefield District CID, said: “We are investigating the death this morning and are appealing for any witnesses who may have seen the male and female in the Bull Ring area prior to midnight or who may have any information.
“While a cause of death will be determined by a post mortem, initial indications suggest it is drug related.
“We would always encourage anyone who has taken an illegal drug or stimulant to urgently seek medical advice if they feel unwell.
“Any witnesses or anyone who has information about the incident is asked to contact Wakefield CID on 101 referencing log number 0022 of April 26.”