The actor was found inside a vehicle parked on the street in Seoul's mid-northern Seongbuk district, an official from the Seongbuk police station told AFP.
"We believe his body has now been transferred to the Seoul National University Hospital," he added.
South Korea's Yonhap news agency reported, citing police, that Lee had left a "note that reads like a will".
Lee had been under police investigation over his alleged use of marijuana and other drugs.
Once celebrated for his wholesome image, local news outlets reported that the actor was being dropped from television and commercial projects following the scandal.
A graduate of South Korea's prestigious Korea National University of Arts, Lee made his acting debut in 2001 in a television sitcom titled "Lovers".
He later won acclaim for his performances in a variety of roles, including a charismatic chef and a genius neuroscientist who is unable to form empathy towards others.
Lee received widespread critical acclaim for his performance in the 2018 TV drama series "My Mister", for his portrayal of a diligent architectural engineer who, despite facing personal turmoil, steadfastly upheld his sense of responsibility as both an adult and a professional.
Globally, he is best known for his portrayal of the wealthy and shallow patriarch in director Bong Joon-ho's 2019 Oscar-winning film "Parasite".
He was also recognised for his performances in romance flicks, such as 2007 TV drama "Coffee Prince" and the 2012 film "All About My Wife".
His last film, this year's horror flick "Sleep" -- in which he played a husband whose sleepwalking eventually leads to horrifying circumstances -- was well-received critically and featured in the Critics' Week section at the Cannes festival.
Devastated fans expressed their grief through messages on social media, with one user writing on X: "I laughed and cried a lot while watching your acting. Thank you."
Lee's reputation suffered a significant blow when South Korean authorities launched an investigation into his alleged drug use in October.
From December 23 to 24, he attended his third police investigation session, which lasted 19 hours, Yonhap reported.
He briefly spoke to reporters in late October before entering a police station in Incheon to meet with investigators.
"I sincerely apologise for causing great disappointment to many people by being involved in such an unpleasant incident," he said at the time.
"I feel sorry for my family, which is enduring such difficult pain at this moment.
"Once again, I sincerely apologise to everyone."
South Korea has extremely tough laws on illegal drugs, with Koreans who take drugs such as marijuana legally abroad risking prosecution upon returning to their home country.
This year, President Yoon Suk Yeol called for more stringent measures to eliminate drug traffickers, saying the country was no longer "drug-free".
Lee is survived by his wife, actress Jeon Hye-jin and two sons.
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