Down when lacking energy - that's a setback (4)
I believe the answer is:
blow
This might be a double definition.
'down when lacking energy' is the first definition.
'blow' can be an answer for 'down' (thesaurus). I'm not sure about the 'when lacking energy' bit.
'setback' is the second definition.
(blow can mean a setback or difficulty)
'that's a' is the link.
Can you help me to learn more?
(Other definitions for blow that I've seen before include "fluff" , "'..., ..., thou winter wind' (As You Like It)" , "Cease to be a problem" , "Setback" , "Waste" .)