The lockdown restrictions will take effect in the Cardiff and Swansea regions, as well as Yanili town.
It will go into effect in Yaneli, Carmarthenshire, on Saturday at 18:00 GMT and in the two largest cities in Wales on Sunday from 18:00.
This means that 1.5 million people, about half of the population, will be under lockdown.
But Health Minister Vaughan Gething said that cases in Kerveli, the first area to be closed, had decreased dramatically.
The restrictions will be the same as those already affecting people who live in Merthyr Tydfil, Bridgend, Blaenau Gwent, Newport, Rhondda Cynon Taf and Caerphilly, which are already closed.
Githing said people in Cardiff and Swansea should not “treat this weekend as a big blast.”
He also said cases in Carmarthenshire have been linked “largely” to Planelli, with eight out of 10 cases there.
“In Llanelli we have a special challenge around the city that has been well defined, and it’s a massive spread that is not under control,” he told a Welsh government press conference.
“We spoke to the local authority, spoke to the local health board, and we understand the need to act and act as quickly as possible.
“If the prevalence rates were the same in Cardiff and Swansea, the infection rates would be much higher.”
He described the “balanced judgment” that was made that the rules should go into effect in Cardiff and Swansea the following day “to allow people to plan.”
In the past seven days, 85 of the 109 cases were in Carmarthenshire in Yaneli with an infection rate of 151.6 per 100,000 people, compared to 57.7 in the wider county.
The Llanelli lockdown is the first to not cover a complete local authority area. Githing said that a postal code finder will be available online to clarify which areas are subject to lockdown.
The majority of cases in Llanelli have been linked to people who socialize without social distancing.
Burry Port, also found in Carmarthenshire, will not be included in the restricted area.
What about university students?
As students return, Mr. Githing said the impact on the dormitories will be watched.
He said, “One of the things we have to do is understand how the pattern changes within those college towns and cities once the students have been there for a while.
“At this point in time with a large movement of people across the UK, we need to understand what this does in terms of local spread, so I don’t think the time has come to make a final decision about what will happen at the end of your vacation but that’s an obvious question for us. To think about it. “
What can I do?
Under the rules, no one is able to enter or leave the eight provinces and one town Without a “reasonable excuse”.
People are allowed to travel outside the area for a limited number of reasons.
This includes going to work if they cannot work from home, going to school, providing care, and purchasing food or medical supplies.
What about unclosed areas?
Ministers and officials said they will look at the data over the weekend before deciding whether the restrictions need to be extended to Neath Port Talbot, Glamorgan Valley and Turfen.
Next week there will be meetings with council leaders in North Wales, with Mr. Githing saying the picture is “more mixed.”
Only part of Carmarthenshire will be closed from Saturday.
“It is alarming to see the extent of the sharp rise in the number of positive cases in Yanili district, and measures had to be taken to help stop the spread and break the chain of infections concentrated in this area to prevent the entire province from being secured,” said Leader Emlin Dole.
“We must all do the right thing, follow advice and protect each other. In parts of Llanelli, we’re asking people and companies to make greater sacrifices – we fully appreciate the impact that will have, but there is no other way. We must stop the spread.”
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