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Gillingham were second-best at Grimsby and have now lost back-to-back games in League 2.
First-half goals from Niall Maher and Gavan Holohan left Gillingham - who had won their first four in the league - with it all to do at Grimsby on Saturday and there was no coming back from the two-goal deficit.
Jayden Clarke was rewarded with a starting role for the Gills following his impressive midweek exploits at Luton Town in the cup but it was Grimsby’s attacking players who bossed it from the off.
Connor Mahoney was cup-tied for the Tuesday clash and was back involved as one of five changes to that team which had given Luton a fright.
The Gills had been boosted by a super second half at Luton. but the opening half at Grimsby was more like the previous weekend, when they were beaten 3-0 at home by Colchester United.
Grimsby looked the brighter of the two teams and after the Gills had cleared away a couple of early corners into the box, it was from another one of those that the defence was undone, with 12 minutes gone.
Corner-taker Arthur Gnahoua picked out the run of Maher, who had got away from Max Ehmer, and his near-post header beat keeper Jake Turner.
Ashley Nadesan put a shot wide for the Gills and almost got in a couple of times but Grimsby always looked the more convincing in attack. They doubled their advantage in the 28th minute.
Gillingham defender Ogie was dispossessed by Danny Rose deep in his own half out wide, and from a right-sided cross, Abo Eisa picked the ball up in a dangerous area and laid it off for Holohan, who had ran past Shaun Williams to come up in support, and he placed the ball past Turner.
Connor Mahoney fired wide for the visitors but Gillingham didn’t look like troubling home keeper Jake Eastwood for the remainder of the half.
The afternoon got worse before the break as striker Tom Nichols limped off injured.
Gills boss Neil Harris made two more changes at the break with Conor Masterson and right-back Cheye Alexander introduced. Shuan Williams left the field and Robbie McKenzie took over his role infront of the defence while Masterson was a straight swap for Ogie in the centre.
Grimsby were straight back on the attack in the second half and it needed a good save low down from Turner to deny Harry Clifton. The hosts continued to put the Gills under pressure as the home crowd sensed a third goal.
With just over 20 minutes left Harris turned to his bench again as Jonny Williams was thrown into the mix. It was at a stage where the Gills had threatened a couple of times down the right flank. At that time there was still hope.
Turner had to make another save, denying the ever-dangerous Eisa, as the hosts remained on top until the final whistle.
A header from Scott Malone almost got the Gills back in it with 87 minutes gone but Eastwood saved – his first real work of the match. The Gills ended with another injury worry after Tim Dieng picked up a knock following a heavy challenge.
Grimsby: Eastwood, Rodgers, Eisa, Holohan (Andrews 89mins), Gnahoua (Pyke 89mins), Clifton, Amos, Mullarkey, Maher, Rose, Conteh. Subs not used: Cartwright, Efete, Waterfall, Hunt, Khouri.
Gillingham: Turner, McKenzie, Malone, Ehmer, Ogie (Masterson 46mins), S Williams (Alexander 46mins), Dieng, Clarke (J Williams 70mins), Mahoney, Nichols (Bonne 44mins), Nadesan. Subs not used: Morris, Clark, Sithole.
Referee: Adam Herczeg
Attendance: 6,479 (407 away)