seriously; joking aside; in all seriousness
Used to preface a sincere statement, often after a lighthearted exchange, to signal that what follows is meant earnestly.
Seriously, you really helped me out.
Joking aside, you'd better drop that topic.
Means 'seriously' or 'earnestly' as an adverb, but lacks the 'joking aside' nuance; 冗談抜きで explicitly sets aside prior joking.
Compound of 冗談 (joke) + 抜き (omitting, without) + で (particle), literally 'without jokes'.