France will look to finish the season strongly against winless Italy in the early kick-off on Saturday, in what looks a fascinating encounter.
After that Wales look to secure a first Grand Slam and Championship triumph since 2012, but Ireland are also hoping they can secure the title themselves to spoil the party.
England face Scotland in the tournament’s final game, hoping results elsewhere will allow them a chance to secure the Championship.
With a host of Guinness PRO14 players set to be involved, here are the main talking points.
Kearney and O’Brien return but Wales unchanged
Warren Gatland has kept faith in the side that beat Scotland last week as he looks to secure his third Grand Slam triumph.
This means Adam Beard keeps his place in the second row and is joined by Ospreys teammates George North, Justin Tipuric and Alun Wyn Jones – who captains Wales – in the starting XV.
Influential Scarlets pairing Hadleigh Parkes and Jonathan Davies will be hoping they can have the same impact as they did in the Scotland game as they kept their places in midfield.
Joe Schmidt has turned to Leinster’s Sean O’Brien and Rob Kearney as they look to spoil Wales’ party at Principality Stadium.
CAPTAIN'S RUN 🏉 “This is what you dream of,” says Alun Wyn Jones as Wales have one final @principalitysta run-out before competing for the #GuinnessSixNations title tomorrow in Cardiff. #WALvIRE pic.twitter.com/UzjsItySG7
— Welsh Rugby Union 🏉 (@WelshRugbyUnion) March 15, 2019
Ulster’s Rory Best will hope to mark his 64th and final Guinness Six Nations appearance by captaining them to victory, and he is joined again by his Ulster teammate Jacob Stockdale.
Schmidt has also handed a Guinness Six Nations debut to Munster second row Tadhg Beirne, and he joins four of his Munster teammates in playing from the start.
Six changes for Scotland in Calcutta Cup clash
England will have their sights on securing the Championship title but their opponents will be desperate to stop them doing so as the two rivals face off at Twickenham.
Scotland will be hoping for a repeat of this match-up 12 months ago where they sensationally won it at BT Murrayfield but England will be going all out to avoid a repeat.
Glasgow Warriors’ Sam Johnson returns to start at centre in place of clubmate Peter Horne.
Edinburgh openside Hamish Watson will be hoping to have a similar impact to last week as he comes in to start, while clubmate lock Ben Toolis also comes in.
Eddie Jones has made four changes to his side as he brings in Jack Nowell, Henry Slade, Ben Moon and Mark Wilson.
📸 @Scotlandteam visit Twickenham for team run ahead of tomorrow's Calcutta Cup clash in the final round of the Guinness Six Nations.
— Scottish Rugby (@Scotlandteam) March 15, 2019
Benneton’s Zanon in line for debut
21-year-old Bennetton centre Marco Zanon is in line to make his Italy debut as head coach Conor O’Shea has made five changes for their clash with France.
Zanon joins eight of his Bennetton Rugby clubmates as The Azzurri look to finish the tournament on a high.
Zebre lock David Sisi also comes in in place of Bennetton’s Dean Budd and he joins Zebre clubmates Andre Lovotti and Edoardo Padovani in the starting XV.
France’s Wesley Fofana returns to make his final Guinness Six Nations appearance and is one of six changes made by head coach Jacques Brunel.
France will be also be desperate to finish on a high after last week’s defeat at the hands of Ireland.