Hampshire 164 for 6 (McDermott 47, Hollman 2-12) beat Middlesex 159 for 7 (Holden 53, Higgins 43, Turner 3-30) by five runs
Hampshire seamer John Turner starred with three wickets on his Vitality Blast debut as the defending champions recorded their third straight win, holding off rock-bottom Middlesex at Radlett.
The 22-year-old captured the wicket of Middlesex captain Stephen Eskinazi with his first ball in the tournament, finishing with 3 for 30 as the Hawks successfully defended a modest total of 164 for 6.
Max Holden's first Blast half-century of the summer, with 53 from 31 balls, had given the Seaxes hope of finally breaking their duck in the South Group as he and Ryan Higgins (43 from 35) added 60 for the fourth wicket.
But Hampshire's death bowlers held their nerve to ensure the home side remain winless in the competition, equalling their longest losing start to a campaign of seven defeats in 2006 and 2009.
Hampshire skipper James Vince, who had smashed a match-winning 88 not out in the sides' first meeting of the tournament, missed out this time after driving Josh de Caires' second ball tamely to mid-off.
But Ben McDermott was soon into his stride, pummelling Blake Cullen for successive boundaries and dispatching both Tom Helm and de Caires over the fence as he and Toby Albert shared a partnership of 56 from 38.
Luke Hollman's tight three-over stint of 2 for 12 broke the stand, luring Albert into a mistimed reverse sweep and the leg-spinner also prised out the big-hitting McDermott, caught at long-off just short of his half-century. With Joe Weatherley and Aneurin Donald both holing out as de Caires recorded his best T20 figures of 2 for 34, the Hawks had lost three wickets for just 11 runs and they responded by shifting Chris Wood up the order to No.7.
That move paid off as the quick hrashed 31 from 21 and he and Ross Whiteley, with an unbeaten 28 from 20, hauled Hampshire above 150 but Higgins, with four consecutive dot balls in the penultimate over, ensured they fell short of par.
However, their total looked more than substantial after two overs of the Middlesex reply, with just two extras on the board and both openers back in the pavilion with ducks against their name.
Eskinazi was caught miscuing a pull to midwicket off Turner's first delivery and Joe Cracknell followed five balls later, leg before - but Holden and Pieter Malan kick-started the innings with a stand of 43 from 23.
Malan, having advanced to 18 with two powerful leg-side blows off Wood, attempted to do the same against Nathan Ellis just before the end of the powerplay and was caught in the deep.
Holden displayed a knack of picking out the gaps, carving Scott Currie to the cover boundary and clipping his next ball to leg for four more as Middlesex kept pace with the required run-rate.
The left-hander brought up his 50 from 26 balls and Higgins was a more than capable foil in their partnership, bisecting the leg-side fielders perfectly to register successive fours off Wood.
But Liam Dawson tilted the contest back in Hampshire's favour, tempting Holden to top-edge a pull to short fine leg and Turner claimed his third wicket before Vince raced from mid-off and dived to pouch a skier from Higgins.
Despite two boundaries by Martin Andersson to keep Middlesex in contention, a target of 15 from the final over proved too steep.