Bridgend, Blaenau Gwent, Merthyr Tydfil and Newport will go into lockdown with people living there facing tougher restrictions after a spike in Covid-19 cases.
Alongside Caerphilly and Rhondda Cynon Taf - where localised lockdown measures have already been introduced - it means more than 840,000 people in Wales will be living under tougher restrictions.
From 6pm on Tuesday, people in the four local authorities will not be able to enter or leave the area without a reasonable excuse, such as travel for work or education.
People will also no longer be able to meet members of their extended households indoors and pubs, bars and restaurants will have to shut by 11pm.
Health Minister Vaughan Gething made the announcement at a Welsh Government press conference on Monday and said he will hold an urgent meeting tomorrow with all local authorities, health boards and police forces in south Wales to discuss the "wider regional situation."
He said Welsh Government were taking this "targeted action" now but further measures could be introduced in the future to different regions if the situation worsens nationally.
The health minister said the high rate in Merthyr Tydfil was focused around two clusters linked to a larger employer and pub.
In Newport the rise in cases is linked to a house party at the end of August but there are now "wide spread cases across the city."
Watch the full press conference here:
Mr Gething also said there were concerns in Bridgend about a "sharp rise" in cases which mirrored the pattern seen in Rhondda Cynon Taf.
He said that while cases in Blaenau Gwent were linked to pubs and a lack of social distancing, there had also been cases in care home staff and in secondary schools in the area.
The number of confirmed Covid-19 cases per 100,000 population has risen in Bridgend, Blaenau Gwent, Merthyr Tydfil and Newport over the last seven days.
The case rate in Rhondda Cynon Taf has also risen despite it being placed under further measures last week.
The health minister said the trend in Rhondda Cynon Taf has changed from mainly younger age groups to now seeing people of all ages infected. He said there are now 34 people with coronavirus in the Royal Glamorgan Hospital which he described as "particularly worrying."
Caerphilly is the only area on the Welsh Government's list to see a drop in cases.
There were already additional restrictions in place for people living in Caerphilly county and Rhondda Cynon Taf after a spike in Covid-19 cases there over the last two weeks.
Caerphilly was the first county in Wales to be put under a local lockdown with Rhondda Cynon Taf following suit last week.