The most common and most likely answer to this crossword clue is the 7 letter word CALMEST
I've seen this crossword clue in The Daily Telegraph
C
A
L
M
E
S
T
Buddy explains!
The straight part
We know that "Most serene" is the straight/definition part of the clue. The straight part is often a synonym or definition, in this case most serene = calmest.The cryptic/wordplay part
In cryptic crossword there's often an wordplay/cryptic part as well.This part involves a more complex hint, such as an anagram, homophone, hidden word, etc.
Sadly, We don't have an explanation for this specific crossword clue yet.
What does CALMEST mean?
CALMEST verb- To make calm.
- To become calm.
- (of a person) Peaceful, quiet, especially free from anger and anxiety.
- (of a place or situation) Free of noise and disturbance.
- (of water) with few or no waves on the surface; not rippled.
- Without wind or storm.