This is a second spell away from Blues for Academy graduate O'Keeffe.BCFC
The loan period runs until the end of the 2019/20 campaign and Blues have a recall provision in place for January 2020 should it be required.
The 21-year-old has permission to play in cup competitions for The Silkmen.
Macclesfield, who are managed by former England defender Sol Campbell, narrowly avoided relegation out of the EFL last season after finishing in 22nd spot in League Two.
This is a second spell away from Blues for Academy graduate O'Keeffe. The Republic of Ireland Under-19 international spent the first four months of last season out on loan with local National League club Solihull Moors, for whom he made 16 appearances.
He also figured 18 times for Blues Under-23s last term, scoring three times.
To date, his one senior appearance for Blues was in the Championship away defeat at Newcastle on 10 December 2016 after coming on as a late substitute.