One issue is that the result is clouded by an extra bogus match. Only one of the 'tail' matches is required. Adding the second one is really bad news for the single regex variant. Choosing to 'nibble' (\s) instead of swallowing whole (\s+) does the single regex a huge disservice too. Consider the following benchmark:

                 Rate sExNibble singleNibble mExNibble  multi multiNib
+ble single
sExNibble      1795/s        --         -74%      -99%   -99%        -
+99%   -99%
singleNibble   6881/s      283%           --      -95%   -95%        -
+97%   -98%
mExNibble    134665/s     7403%        1857%        --    -5%        -
+49%   -60%
multi        142315/s     7830%        1968%        6%     --        -
+46%   -58%
multiNibble  263146/s    14562%        3724%       95%    85%         
+ --   -22%
single       338640/s    18769%        4822%      151%   138%         
+29%     --
[download]

Some other points: I think you want ^\s not \^s, and your alternation form does not terminate the replacement part of the substitution (i.e., you're missing the last '/').

yes I have a typo in the post. It shoud be ^\s, but that still doesn't give me an answer. Why does it run slower than running all three substitutions on different lines?

Why does it run slower than running all three substitutions on different lines?

Because the first three are all optimisable; they are all explicitly anchored to the beginning or end of the string, and the regex engine is smart enough to try the match only at the beginning or end of the string, respectively.

The combined pattern is too complex to be optimised, so the engine naively tries matching at every position in the (long) string.

Dave.

yes I have a typo in the post. It shoud be ^\s, but that still doesn't give me an answer.

If you fix that typo and then run Benchmarks, I think you will see that they are about the same speed. I see speed differences of 0-3% with the typo fixed, and 20-25% with the typo in place.... probably because some optimization is possible when the regex says "beginning of string" and not '^' in an arbitrary place in the string.

Your first three regex do not need the modifier /g. You are using anchors, so the /g modifier is useless here. If you leave it out, the work will be done faster...

Your second regex (one whitespace at the end of line/string) is redundant, because it is already included in the third regex (one or more whitespace(s) at the end of line/string).

You really want to remove all whitespaces from the end of line, but only one from the beginning?

$string =~ s/^\S+//;  # assumed to remove *all* whitespaces from the b
+eginning
$string =~ s/\S+$//;  # assumed to remove *all* whitespaces from the e
+nd

$string =~ s/^\s+|\s+$//g;  # /g needed here
[download]

Benchmark:

#!/usr/bin/perl
# vi:ts=4 sw=4 et:
use strict;
use warnings;

use Benchmark qw( cmpthese );

my $results = cmpthese(
    -3, {
        'r2/g' => sub {
            my $string = ( ' ' x 1000 ) . 'x' . ( ' ' . 1000 );
            $string =~ s/^\s+//g;
            $string =~ s/\s+$//g;
        },
        'r2' => sub {
            my $string = ( ' ' x 1000 ) . 'x' . ( ' ' . 1000 );
            $string =~ s/^\s+//;
            $string =~ s/\s+$//;
        },
        'r1' => sub {
            my $string = ( ' ' x 1000 ) . 'x' . ( ' ' . 1000 );
            $string =~ s/^\s+|\s+$//g;
        }
    }
);
[download]

Result:

         Rate   r1 r2/g   r2
r1   135605/s   -- -19% -25%
r2/g 168081/s  24%   --  -7%
r2   181494/s  34%   8%   --
[download]

If your text in $string is multilined, you should check perlre for the /m modifier.

update: fixed typo.