Nkaissery, 67, died a few hours on Saturday morning after being admitted at the Karen Hospital.
Head of public service Joseph Kinyua confirmed the sudden death in a statement to the newsrooms on Saturday.
“It is with deep sorrow and shock that we announce the sudden death of Interior CS Joseph Nkaissery, the country will be updated as more information becomes available,” the statement read.
On Friday, Nkaissery accompanied President Uhuru Kenyatta at Uhuru Park grounds for the Saba Saba prayers before holding a series of meetings at his Harambee House office in the afternoon.
Nkaissery served in the military for 29 years where he ascended to the rank of Major General.
He later joined politics in 2002.
In 2007, Nkaissery was elected a member a parliament for Kajiado Central on an ODM ticket.
He served as Assistant Minister for Internal Security in the Grand coalition government between 2008-2013.
In November 2014, President Uhuru appointed Nkaissery as Interior CS to replace Joseph Lenku who was sacked for failing to secure the country following two massacres by the al Shabaab.