Xavi's side have won both of their European outings so far this season - thrashing Antwerp 5-0 before earning a 1-0 triumph away to Porto last time out - and could underline their status as Group H top dogs when Shakhtar come to town.
The Ukrainian outfit were beaten by Porto in their opening match of the group, but launched a memorable comeback from 2-0 down to win 3-2 against Antwerp last time out.
However, the visitors may be something of an unknown quantity heading into this match following the appointment of Marino Pusic as their new manager on Tuesday.
Here, Sports Mole takes an in-depth look at the head-to-head record and previous meetings between the two sides.
Head-to-head record
Previous meetings: 9
Barcelona wins: 6
Draws: 2
Shakhtar wins: 1
These two sides have been relatively familiar foes in recent years, with Wednesday's match their 10th meeting overall and eighth in the last 20 years - six of which current Barca boss Xavi featured in as a player.
Unsurprisingly, Barcelona edge the overall head-to-head record with six wins to Shakhtar's two from those nine previous meetings, including each of the last three in a row.
The most recent of those came in the 2010-11 Champions League quarter-finals, when unsurprisingly Lionel Messi had the decisive say with the only goal of the game in the return leg.
The tie had already been largely settled by that stage courtesy of Barca's 5-1 triumph in the first leg, courtesy of goals from Andres Iniesta, Dani Alves, Gerard Pique, Seydou Keita and Xavi.
There has been silverware on the line in one previous meeting between the two teams, with Barcelona winning the 2009 UEFA Super Cup in Monaco, although they needed extra time before Pedro netted the only goal of the game.
That meeting came the season after they had met in the Champions League group stage, when Shakhtar picked up their most recent victory over the Spanish giants - and their only away triumph over them - courtesy of goals from Oleksandr Gladkyy (2) and Fernandinho in a 3-2 win.
Shakhtar ultimately finished third in that group to drop into the UEFA Cup, which they duly won, while Barcelona went all the way in the Champions League, beating Manchester United in that season's final.
There was also one win apiece in the 2004-05 Champions League group stages, with Deco, Ronaldinho and Samuel Eto'o on the scoresheet in Barca's home win and a Julius Aghahowa brace handing Shakhtar their first-ever win over the La Liga side.
The first meetings between the two sides saw Barcelona run out 4-1 aggregate winners in the first round of the 1978-79 European Cup Winners' Cup, with Hans Krankl scoring in both games.
Barcelona have won eight of their previous 11 home games against Ukrainian opposition in total, while home or away they have won each of their last nine meetings with teams from the country.
Shakhtar, meanwhile, have been regular opponents for Barcelona's bitter rivals Real Madrid in recent seasons and have won four of their last 10 visits to Spain.
Overall, though, have lost 17 and won only seven of their 31 previous games against La Liga opposition.
Previous meetings
Apr 12, 2011: Shakhtar Donetsk 0-1 Barcelona (Champions League quarter-final second leg)
Apr 6, 2011: Barcelona 5-1 Shakhtar Donetsk (Champions League quarter-final first leg)
Aug 28, 2009: Barcelona 1-0 Shakhtar Donetsk (UEFA Super Cup)
Dec 9, 2008: Barcelona 2-3 Shakhtar Donetsk (Champions League group stage)
Oct 1, 2008: Shakhtar Donetsk 1-2 Barcelona (Champions League group stage)
Dec 7, 2004: Shakhtar Donetsk 2-0 Barcelona (Champions League group stage)
Sep 29, 2004: Barcelona 3-0 Shakhtar Donetsk (Champions League group stage)
Sep 26, 1978: Shakhtar Donetsk 1-1 Barcelona (European Cup Winners' Cup first round second leg)
Sep 12, 1978: Barcelona 3-0 Shakhtar Donetsk (European Winners' Cup first round first leg)
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