Both changes are in the backs, with winger Fetu'u Vainikolo coming in for Ryan Shortland, and Andrew Parata replacing the injured Luke Herden at second five-eighth.
Herden injured a thigh in the win over North Harbour last week and was forced off the field near the end of the first half.
Aaron Bancroft comes on to the bench and may make his first appearance for Otago this season.
James Kenny is the reserve halfback and will make his first-class debut if he gets on the paddock. Johnny Legg is out for two to four weeks with an ankle injury.
Shortland had a quiet game against Harbour, and coach Steve Martin said Vainikolo was an experienced winger who deserved his chance after playing well for Otago B.
"Ryan has really impressed in the first couple of games he has played for Otago but Fetu'u has been around the traps and showed good form in a couple of games for Otago B," Martin said.
Prop Kees Meeuws returns to the bench after flu ruled him out last week.
Manawatu has also made just two changes, with players overcoming niggling injuries to make it on to the field.
Former Otago prop Grant Polson has by a back injury and has been replaced on the loosehead side by the experienced Talau Hala.
Blindside flanker Nick Crosswell, who captained the side last week, is out with a hamstring injury and has been replaced by Hamish Gosling.
Josh Bradnock, who is the regular skipper but is returning from injury, will captain the side.
Manawatu ended its game last week with golden oldies scrums in force and its bench cleared, but doubts over players have eased, with midfield back Tevita Taufau having recovered from a nasty blow to the face.
Hooker Sean O'Connor has recovered from an Achilles heel injury, while prop David Te Moana has shrugged off an ankle injury.
Palmerston North is something of a homecoming for some in the Otago team.
Lock Hayden Triggs played all his first-class rugby for Manawatu until this year, while other members of the team played in the city for the Highlanders when the southern franchise had an impressive win over the Bulls earlier this year.
Martin said the city was not quite a second home, but it was familiar to some members of the team.
"But this is a different team with their own history to create."
Manawatu finished last in 2008 but has already won more games than last year, beating Counties-Manukau, then defeating Southland in an upset win last Friday night.
Martin said spirits had lifted in the Otago side after its first win of the season last week, but it was not taking Manawatu lightly.
Otago will travel to Whangarei next week to play Northland after Okara Park was cleared for play.
Poor ground conditions resulting from wet weather had led to the park in Whangarei being deemed unsuitable for play, and the match between Northland and Taranaki on August 6 was switched to North Harbour Stadium.
Martin said yesterday the ground had been given the all-clear and would host the match, on August 28.
MANAWATU v OTAGO
- Palmerston North, tomorrow, 7.35pm
Otago: Ben Smith, Karne Hesketh, Brett Mather, Andrew Parata, Fetu'u Vainikolo, Chris Noakes, Sean Romans, Steven Setephano, Alando Soakai (captain), Adam Thomson, Tom Donnelly, Hayden Triggs, Sam Hibbard, Jason Macdonald, Ben Nolan.
Reserves: Peter Mirrielees, Kees Meeuws, Hoani Matenga, Paul Grant, James Kenny, Glenn Dickson, Aaron Bancroft.
Manawatu: Kurt Baker, Andre Taylor, Tevita Taufai, Johnny Leota, Casey Stone, Aaron Cruden, Aaron Smith, Brent Thompson, Josh Bradnock (captain), Hamish Gosling, Reece Robinson, Michael Fitzgerald, David Te Moana, Sean O'Connor, Talau Hala.
Reserves: Rob Foreman, Adrian Barone, James Goode, Doug Tietjens, Isaac Thompson, Aaron James, Lote Raikabula.