Generally speaking, the married filing separate status will give the same result, whether filing with the current spouse or a new spouse.
One thing you may have to change is whether to use standard or itemized deductions.
When filing separately, both spouses must do the same thing — either both use the standard deduction, or both itemize.
You want to be sure that the selection of “standard” or “itemized” that you use for the party is the same as that selection for the new spouse.
If a party’s filing status is “Married filing separately,” click Enter Data > Parties & Children, and you will see the link that is highlighted below.
Click the link at “Click here if parties are both ‘married filing separate’ in the current year. You will be taken to the screen shown below.
At the bottom of that screen is the place where you choose whether to use the standard or itemized deduction.
The software is assuming that the party is filing separately with the current spouse, and it automatically calculates which is better. To do that, it looks at which choice minimizes the total of the two parties’ taxes.
Because the party will be filing separately with a new spouse, you may need to override this calculation, to indicate whether the party will be using the standard deduction or itemizing.