Does using portable programs or especially LiberKey slow down the computer?

No.

Using portable applications don't inflate the Windows' registry like installed programs.

JP4U

OK, many thanks.

It can slow down the whole computer if the application access an USB key which have a slow USB controller which handle slowly hardware interruptions.
It can also occurs if the application read or write really lots of files on an USB key (not relevant for internal drives) and Liberkey Menu is known to read often at startup (but not after) and if your anti-virus is a little bit slow (because you start the computer and all services are starting at the same time).

But this is just assumptions, please precise your symptoms.

JP4U wrote:No.

Using portable applications don't inflate the Windows' registry like installed programs.

JP4U

I mostly use portable applications to keep my Registry as well as system folder clean.