China has reacted angrily to Canada's arrest on Dec. 1 of Chinese executive Meng Wanzhou, the chief financial officer of China's Huawei Technologies, and Spavor's disappearance is likely to further escalate the diplomatic row.
Meng's arrest was made at Washington's request. She has been accused by U.S. prosecutors of misleading banks about transactions linked to Iran, putting the banks at risk of violating sanctions.
Canada has been unable to contact Spavor since he notified the Canadian government that he was being questioned by Chinese authorities, Foreign Ministry spokesman Guillaume Berube said in statement issued in Canada late on Wednesday.
Canada was working hard to ascertain Spavor's whereabouts and would continue to raise the issue with the Chinese government, Berube said.
Canadian Foreign Minister Chrystia Freeland earlier told reporters that a second Canadian citizen could be in trouble in China.
Phone calls, messages and emails to Spavor went unanswered on Thursday.
Friends of Spavor told Reuters he was due to fly out of Dalian on a Korean Air flight to South Korea at 2:05 p.m. (0605 GMT) on Monday but had not arrived.
Spavor, who is based in the northern Chinese city of Dandong, on the border with North Korea, is the head of Paektu Cultural Exchange, a China- and UK-based non-profit social enterprise.
The group says on its website it is "dedicated to facilitating sustainable cooperation, cross-cultural exchanges, activities, trade, and investment" with North Korea.
It also says the organisation maintains an "array of contacts" within North Korea and is "nonpolitical."
Spavor has acted as a translator and facilitator for former U.S. National Basketball Association star Dennis Rodman on trips to North Korea and shared Long Island Iced Teas with North Korean leader Kim Jong Un on board one of his private boats after they went jet-skiing in 2013.
More recently he has been trying to facilitate investment in North Korea in anticipation of sanctions being lifted, often hosting both North Korean officials and potential investors at his office in Dadong as well as on trips inside North Korea, Spavor told Reuters in previous interviews.
— CNBC contributed to this report.