Scrum-half John Cooney has been recalled to Ulster's starting line-up as the Irish province make four changes for their Champions Cup quarter-final clash with Toulouse on Sunday.
Jack McGrath comes in at loosehead prop, with Jordi Murphy and Nick Timoney coming into the back row.
Marcell Coetzee misses the game through an injury sustained against Leinster.
Prop Eric O'Sullivan and back row Matthew Rea join Mathewson in dropping to the replacements' bench.
Ulster are aiming to make the semi-finals for the first time since 2012, when they went on to lose 42-14 to Irish interprovincial rivals Leinster in the final.
Dan McFarland's side are contesting the last eight of Europe's premier club competition for the second year in a row, having been edged out by Leinster 21-18 in a thrilling quarter-final in Dublin 18 months ago.
The inclusion of Murphy and Timoney in the starting team means that Sean Reidy makes a positional switch to blindside flanker for the encounter with the Top 14 outfit.
The match with Toulouse had originally been scheduled to take place on 5 April but was postponed for several months because of the coronavirus pandemic.
The game was to be played at the 33,000-capacity Le Stadium but the venue was moved earlier this month to the Stade Ernest Wallon because of Covid-19 restrictions.
The Stade Ernest Wallon holds up to 19,000 people but attendance will be limited to 5,000 for the Ulster game because of restrictions on gatherings.
Ulster won both fixtures when the sides met in the pool stages of the competition in December 2015.
Toulouse topped Pool Five of this year's competition with six wins from six outings, while Ulster won five out of six in finishing second behind Clermont Auvergne in Pool Three.
The winners of the tie will play Exeter or Northampton in the semi-finals.
Toulouse: Ramos; Huget, Guitoune, Ahki, Kolbe; Ntamack, Dupont; Baille, Mauvaka, Faumuina, Arnold, Tekori, Kaino (capt), Cros, Tolofua.
Replacements: Marchand, Neti, Aldegheri, Meafou, Placines, Holmes, Bales, Lebel.
Ulster: Lowry; Lyttle, Hume, McCloskey, Stockdale, Burns, Cooney; McGrath, Herring, O'Toole; O'Connor, Henderson; Reidy, Murphy, Timoney.
Replacements: Andrew, O'Sullivan, Moore, Carter, Treadwell, Mathewson, Faddes, Matthew Rea.