Its heavily distorted and fuzzy guitars, snarling vocals, blunt bass line and energetic drumming contributed to a dirty sound that influenced many local musicians, and helped develop the nascent Seattle grunge scene.

According to AllMusic, "the song's raw, primal energy made it an instant anthem which still stands as one of [grunge's] all-time classics".

According to Mudhoney vocalist Mark Arm, "Touch Me I'm Sick" originated from a discussion with Sub Pop owner Bruce Pavitt, who "said: 'Hey, you sing about dogs.

[4] Producer Jack Endino was surprised by how noisy the sessions were and how dirty the band wanted the guitars to sound; "for the most part, I just sort of stood back and let them go at it".

[7][8] "Touch Me I'm Sick" has a straightforward garage punk structure with a simple repeating power chord riff played at a high tempo.

[1] Music writer Brian J. Barr referred to this noisy sound as "the sonic equivalent of an amplified comb scraping against paper".

[12] In his book Loser: The Real Seattle Music Story, Clark Humphrey accuses the song of being a copy of "The Witch" by The Sonics.

[1] In an essay called "'Touch Me I'm Sick': Contagion as Critique in Punk and Performance Art", Catherine J. Creswell suggests that some of the lyrics refer to AIDS.

[1][10] Similarly, the music writer Sleazegrinder compares Arm's singing to "a gargly, half-mad howl, the panicky yelp of a rabid dog falling down a well".

Prior to the release of the "Touch Me I'm Sick" single, Pavitt sent a five-song Mudhoney tape to New York alternative rock band Sonic Youth for their opinions.

Sonic Youth's cover was included in the deluxe edition of Daydream Nation (2007), and offers a female perspective of the song with bassist Kim Gordon handling the vocals.

Following the success of the "Touch Me I'm Sick" single in the Seattle area, Sub Pop positioned Mudhoney as the flagship band of their roster and heavily promoted the group.

[22] The band's early material received airplay on college radio and influenced many local musicians, including Kurt Cobain of Nirvana.

Although Mudhoney never attained this level of mainstream acceptance, according to AllMusic's Mark Deming, the band's "indie-scene success laid the groundwork for the movement that would (briefly) make Seattle, WA, the new capital of the rock & roll universe".

Since it did not exist—Arm briefly considered making a fake one by writing down the lyrics, crumpling the sheet, and then burning the edges—the band instead donated Turner's old Big Muff pedals.

[24] First editions of the 7" itself are considered collector's items, "routinely command[ing] three-figure prices", according to Louder magazine in 2016.

[7] A staple of Mudhoney's live set ever since its release, Arm says the band hasn't tired of performing the song: "The beauty of it is that it’s two minutes long.