Two people are feared dead following protests against the Supreme Court ruling in Migori on Monday.
A medic and a clinical officer were reportedly shot dead as they rescued injured protesters.
Residents have intensified secession calls after the Supreme Court ruling upheld President Uhuru's election win.
Youths blocked roads and lit bonfires using tyres in Migori town, Awendo, Rongo and Sori.
George Otoyo said they will not recognise the legitimacy of Uhuru's administration as six out of the county's eight constituencies did not take part in the Octobber 26 poll.
"As far as we are concerned, Migori county should secede from Kenya and form our own country. We have been marginalised as a region since independence," he said.
He said Migori county has been left out in resource and development from the national government, adding that the election was sham and will give them an impetus to secede.
Those protesting said they will only stop after NASA leader Raila Odinga gives them direction.
A demonstrator during protests in Migori over the Supreme Court ruling that upheld President Uhuru Kenyatta's election, November 20, 2017. /MANUEL ODENYNY
Earlier, business people and public service vehicles started normal operations before closing shop hurriedly once the decision was read.
Migori, Kisumu, Siaya and Homa Bay counties did not participate in the repeat presidential election.
Uhuru was declared winner by IEBC with 98 per cent of the vote. Raila pulled out of the election and declared the Jubilee administration illegitimate after Monday's ruling.