"In the event you or your office is required to engage in the IPAB process, would you recuse yourself to avoid creating the impression of a conflict of interest?" the lawmakers wrote.
"At a time of diminished trust in government, it is imperative that we make all efforts to eliminate any appearance of favoritism," they added.
The IPAB was created under ObamaCare to control costs in Medicare. If convened, the 15-member panel would recommend targeted provider cuts if growth in Medicare spending exceeds a certain level.
A recent report by the Congressional Research Service said that Sebelius is required to step in if the IPAB fails to make its recommendations.
Either proposal would be "fast-tracked" through Congress — a situation that has drawn criticism from Republicans who believe it undermines the legislature's role.
It's possible Sebelius may have to step in because Republican congressional leaders have refused to nominate members to the IPAB board.
Cornyn and Roe said this outcome would give her "near-unilateral power to make proposals" that would affect companies she regulates.
Those companies might also include the healthcare interests Sebelius spoke with on behalf of Enroll America, lawmakers said.
The Health and Human Services Department has said that Sebelius's calls were legal, and had precedent in the George W. Bush administration.