A missed penalty in stoppage time made it two away day defeats in a week for the Seasiders.
Gary Bowyer’s players were beaten at Roots Hall thanks to goals in each half from Antony Wordsworth and Simon Cox.
Both were as a direct result of mistakes from Blackpool defender Curtis Tilt and left them playing catch-up.
They halved their deficit through Kyle Vassell’s goal and had a golden chance to level in injury time, only for Jimmy Ryan to see his penalty saved by Mark Oxley..
Bowyer had made the one change from the midweek draw against Rochdale at Bloomfield Road.
Nathan Delfouneso came in on the left-hand side of midfield in place of Callum Cooke as the Seasiders again stuck with the 4-5-1 formation which had served them so well in recent weeks.
Stephen McLaughlin saw an early effort deflected wide of the Blackpool goal before the Seasiders shot themselves in the foot and went behind on five minutes.
Tilt was under no pressure but directed his header behind for a corner; McLaughlin pulled the set piece back and Wordsworth gave Ryan Allsop no chance with his first-time finish.
Tilt could have redeemed himself at the other end moments later but opted to head Ryan’s free-kick across the area rather than test Oxley.
The Seasiders’ defender continued to be the centre of attention as Southend almost doubled their lead on 20 minutes in an almost identical fashion to their first goal.
He brought down McLaughlin on the right-hand edge of the area; McLaughlin again took the set piece but, on this occasion, Wordsworth’s shot was blocked.
However, Blackpool came into the game more as the half progressed even if there was more than the odd pass going astray.
Oliver Turton shot wide and Sessi D’Almeida looped a header over before Oxley was twice called into action either side of the half-hour.
Firstly, he tipped Vassell’s shot onto the post before pushing over Sean Longstaff’s effort from distance.
Nevertheless, it could have been the hosts two goals in front by the break after the Seasiders again squandered possession.
This time, Southend broke with Cox getting into the area before his shot was kept out by Allsop and Tilt cleared the loose ball off the line.
Needing a good start to the second half, Bowyer’s players instead had the worst opening as they conceded a second within the opening minute.
Tilt tried to head the ball back to Allsop, made minimal contact and Cox nipped in to prod home.
Blackpool responded as Turton and Longstaff played a one-two which ended with Turton brought down by Anton Ferdinand as he got his shot away.
The ball went wide of Oxley’s left-hand post and Blackpool’s penalty appeals came to nothing.
Bowyer responded by introducing Will Aimson for Viv-Solomon-Otabor, switching to a back three and seeing his side pull a goal back almost immediately.
Ryan sent a beautiful long pass behind the home defence, Vassell beat Oxley to the ball and rolled it into the empty net.
Try as the Seasiders did to find a leveller, they were unable to breach the home defence for a second time.
Ryan fired a free-kick into the wall and Vassell sent another set piece horribly off target as Blackpool’s efforts veered from the achievable to the ambitious.
No more was that better exemplified than the 60 seconds in which Clark Robertson saw his header turned behind and Colin Daniel attempted to score with a first-time shot from 35 yards.
Then the latest of drama; three minutes into added time, and having seen Tilt’s header cleared off the line, the Seasiders were awarded a penalty after a coming together inside the area.
However, Oxley dived low to his left and kept out Ryan’s penalty to leave the Seasiders heading back north, wondering what might have been.
Southend United: Oxley, Demetriou, Ferdinand, Kyprianou, Timlin, Wright, Leonard, Wordsworth, McLaughlin (White 73), Cox (Robinson 79), Ranger (Fortune 63). Subs not used: Bishop, Hendrie, Yearwood, McGlashan.
Blackpool: Allsop, Turton, Tilt, Robertson, Daniel, Solomon-Otabor (Aimson 54), Longstaff, Ryan, D’Almeida (Cooke 68), Delfouneso, Vassell (Quigley 81). Subs not used: Williams, Mellor, Taylor, Clayton.
Referee: John Brooks.