This will be the first-ever FA Cup meeting between the two sides, and the first of any kind since the Bees beat Vale 2-0 in January 2014 when they were in League One.
For the first time since December 11, Port Vale will be hoping to take to the pitch following postponements against Exeter City and Harrogate Town due to coronavirus.
Darrell Clarke has had to contend with several COVID-19-related issues in recent weeks, but the 44-year-old head coach claimed in his pre-match press conference that he and his team will be as well prepared as they can be to try to cause an FA Cup upset this weekend.
Vale have already beaten two teams in higher divisions to set up their third-round clash with Brentford; an impressive 5-1 first-round victory at home against League One side Accrington Stanley in November was followed by a 2-1 away win at Burton Albion in the second round last month.
The Burslem-based outfit – who are currently sitting sixth in League Two and four points off the automatic promotion places – have been beaten in their last seven FA Cup ties against Premier League opposition, though they previously progressed against both Southampton and Everton back in 1993-94 and 1995-96 respectively.
A surprise upset at Vale Park would see Clarke's men advance to the fourth round for the first time since the 2013-14 campaign.
After three successive Premier League defeats against Chelsea, Brighton & Hove Albion and Manchester City, Brentford claimed all three points at home against Aston Villa last weekend.
Despite trailing through Danny Ings's early opener, Yoane Wissa equalised with a sweet left-footed strike in the 42nd minute, before Mads Roerslev's first-ever goal for the Bees in the 83rd minute helped secure their sixth top-flight win of the season.
Thomas Frank's men have moved up to 12th in the Premier League table, 12 points above the relegation zone and just two points off the top 10.
As fears of an immediate drop back down to the Championship seem to be fading, Brentford may now target an FA Cup run, with a favourable fixture away against League Two opposition to come this weekend in the form of Port Vale.
The Bees have reached at least the fourth round of the FA Cup in each of the last three campaigns, and a victory on Saturday would see Frank's men progress from this stage for the fourth successive season, matching a feat that they last achieved between 1945-46 and 1948-49.
The hosts announced on Thursday that centre-back Ryan Johnson has completed a permanent transfer to National League side Stockport County.
However, January addition Ryan Edmundson, who has joined on loan from Leeds United, could be handed his debut up front alongside Dennis Politic.
As for Brentford, up to eight first-team players could be absent due to injury, while Frank Onyeka is away on international duty with Nigeria for the Africa Cup of Nations.
Frank revealed in his pre-match press conference that Charlie Goode and Mathias Jorgensen will remain on the sidelines for a bit longer, while Saturday's game will also come too soon for Rico Henry, Mathias Jensen, Sergi Canos, Josh Dasilva, Tariqe Fosu-Henry and David Raya.
However, Frank also stated that Bryan Mbeumo, who has missed the last two matches with an injury, is likely to be involved at Vale Park, while Kristoffer Ajer will start in defence as the Bees boss is keen to see the Norwegian build up his match fitness.
Talisman Ivan Toney – who has been directly involved in eight goals in his last seven appearances in the FA Cup, scoring six and assisting two – could be given a rest, with Mbuemo, Wissa and Marcus Forss looking to force their way into the first XI.
Port Vale possible starting lineup:
Covolan; Cass, Smith, Martin; Worrall, Garrity, Pett, Gibbons; Conlon; Politic, Edmundson
Brentford possible starting lineup:
Cox; Ajer, Jansson, Sorensen; Roerslev, Baptiste, Janelt, Bidstrup, Thompson; Mbuemo, Forss
We say: Port Vale 0-2 Brentford
After nearly a month without competitive football, Port Vale players and supporters will be desperate to get back into action and they will be fired up for their challenging encounter against Premier League opposition.
However, the loss of attacking trio Wilson, Proctor and Rodney is a blow for Vale, and although Clarke's men are sure to put up a fight, we expect the hosts to be stung by the Bees on home soil.
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