The southern port city saw temperatures reach as high as 45 degrees Celsius yesterday, just short of an all-time high in the city of 47 C in June 1979.
"Thirty people were brought dead and 15 died shortly after they reached the hospital," Dr Seemin Jamali, the head of the emergency department at state-run Jinnah Hospital, told AFP.
"They all died of heat stroke," she said.
Pakistan's Meteorological Department said temperatures would likely subside in the coming days, but doctors have advised avoiding exposure to the sun and wearing light cotton clothes.
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The high temperatures were made worse by frequent power outages, sparking protests in several parts of the city of 20 million.
Electricity cuts in turn crippled Karachi's water supply system, hampering the pumping of millions of gallons of water to consumers, the state-run water utility said.
Prime Minister Nawaz Sharif has warned electric supply companies that he would not tolerate power outages during Ramadan, an official in Sharif's office said.