O'Shea, who has seen his side go through the opening weeks of the season unbeaten, has opted to swap his hookers for the clash, with Chris Brooker replacing the benched Joe Gray.
That means England scrum-half Danny Care, who scored a try for the A team on Monday, has to be content with a place on the bench as he continues his rehabilitation from a broken toe.
Benjamin Urdapilleta and Tom Williams are also named among the replacements, with the injured Rory Clegg and Matt Hooper making way.
Connacht boss Eric Elwood has shuffled his back division for the trip to Quins.
Eoin Griffin is the only new face among the backs, as he starts in the centres - with Gavin Duffy moving to full-back and Tiernan O'Halloran switching to the wing. Fetu'u Vainikolo is the man to make way.
There are a further two changes in the pack with Ray Ofisa and John Muldoon teaming up with George Naoupu in the back row.
TJ Anderson drops to the bench, where he is joined by former Leeds centre Henry Fa'afili.
Harlequins: 15 Mike Brown, 14 Seb Stegmann, 13 George Lowe, 12 Jordan Turner-Hall, 11 Sam Smith, 10 Nick Evans, 9 Karl Dickson, 1 Joe Marler, 2 Chris Brooker, 3 James Johnston, 4 Ollie Kohn, 5 George Robson, 6 Maurie Faasavalu, 7 Chris Robshaw, 8 Nick Easter.Replacements: 16 Joe Gray, 17 Nic Mayhew, 18 Kyle Sinckler, 19 Tomas Vallejos, 20 Luke Wallace, 21 Danny Care, 22 Benjamin Urdapilleta, 23 Tom Williams,
Connacht: 15 Gavin Duffy, 14 Brian Tuohy, 13 Eoin Griffin, 12 Dave McSharry, 11 Tiernan O'Halloran, 10 Miah Nikora, 9 Paul O'Donohoe, 1 Brett Wilkinson, 2 Adrian Flavin, 3 Rodney Ah You, 4 Michael Swift, 5 Mike McCarthy, 6 John Muldoon, 7 Ray Ofisa, 8 George Naoupu.Replacements: 16 Ethienne Reynecke, 17 Ronan Loughney, 18 Dylan Rogers, 19 Dave Gannon, 20 TJ Anderson, 21 Frank Murphy, 22 Niall O'Connor, 23 Henry Fa'afili,
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