Pompey suffered a nightmare afternoon in Southend, with injuries and suspensions adding to a 3-1 defeat.
Matt Clarke’s own-goal and a Jason Demetriou strike saw the hosts roar into an early lead at Roots Hall.
Gareth Evans reduced the deficit before the break, only to pick up a knock and have to be withdrawn.
Hopes of a comeback were then dashed in the second half, as Nathan Thompson was sent off before Brett Pitman also limped down the tunnel and Demetriou added a third for the Shrimpers.
Kenny Jackett stuck with the same side that were narrowly beaten by Blackburn on home soil earlier in the week.
And it looked to be a good decision as the visitors came flying out of the traps in the warm Essex sunshine.
They should have broken the deadlock when Evans fed Conor Chaplin in the box, but the striker could only fire narrowly past the post.
Instead it was Southend who took the lead against the run of play – and thanks to a large slice of fortune – on six minutes.
Anton Walkes was caught in possession by Shayon Harrison and when Clarke tried to nick the ball from him, he could only succeed in burying the ball into the net.
That saw the confidence levels switch, with Southend unsurprisingly lifted and the Blues looking stunned.
The hosts soon capitalised on that by doubling their advantage, as Demetriou collected a pass from Stephen McLaughlin and lashed the ball home.
They almost added a third goal moments later, but Dru Yearwood’s drive flew inches wide of Luke McGee’s post.
It failed to dampen the spirits of the travelling fans packed into the North Stand, who kept backing their side.
But they were not given much reward, as Pompey struggled to find any kind of fluency going forward.
They managed to reduce the deficit on 36 minutes, however, thanks to good work from Jamal Lowe on the right.
He sent in a teasing cross and Pitman was able to turn it back into the centre, where EVANS was waiting to bundle the ball over the line.
Unfortunately, the winger got injured in the process of scoring and limped off to be replaced by Connor Ronan.
There might have been a leveller in stoppage-time, but Pitman could not quite get on the end of another dangerous delivery from Lowe.
It was Southend who had the final say of the first half, though, and Freddie Lapado should have done better than divert a free header straight at McGee.
Half Time: Southend 2 Pompey 1
Chaplin had a speculative strike that only narrowly missed the target just after the action got back underway.
A Southend break then looked concerning for the Blues, only for McLaughlin to over-hit a pass and the danger to subside.
Lowe was looking lively at the other end of the pitch, but was unable to find the net from an acute angle after leaving his marker on the turf.
It was the visitors now looking the more ambitious side, although they were struggling to test Mark Oxley in the Shrimpers goal.
But Pompey’s task was made much tougher when Thompson caught Ben Coker with a late challenge on 64 minutes and was shown a straight red card by referee Lee Probert.
It almost – and really should have – got worse for them, as Harrison glanced Michael Timlin’s cross wide from a few yards out.
More bad news was just around the corner, though, with Pitman limping off to be replaced by Oli Hawkins.
Southend came close to making their numerical advantage count when McGee failed to claim McLaughlin’s cross.
But the keeper redeemed himself with a superb save using his legs from Simon Cox’s ferocious follow-up.
Lowe was looking the biggest threat for the Blues and after twisting his way into space on the right, the winger’s cross somehow evaded everyone as it flew out of play.
Southend wrapped up the points on 84 minutes, however, as Demetriou collected a pass from Yearwood and rolled the ball home.
Southend (4-4-2): Oxley; Demetriou (Bwomono 90+4), Turner, Ferdinand, Coker (c); McLaughlin, Yearwood, Timlin, Harrison; Cox (Wright 87), Ladapo (Fortune 73)
Goals: Clarke 6 (og), Demetriou 12, 84
Subs not used: Bishop, Kyprianou, McGlashan, Robinson
Pompey (4-4-2): McGee; Walkes, Burgess, Clarke, Donohue; Evans (Ronan 38), Close, Thompson, Lowe; Chaplin, Pitman (c) (Hawkins 69)
Goals: Evans 36
Sent off: Thompson
Subs not used: Bass, Deslandes, Haunstrup, May, Naismith
Referee: Lee Probert
Attendance: 9,397 (1,920 Pompey fans)