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Background Connexin 43 (Cx43) plays a central role in the inflammatory response and wound healing. Targeting Cx43 expression reduces inflammation in a variety of injuries. The expression pattern of Cx43 has not been described for many inflammatory skin diseases. Objectives To describe the expression patterns of Cx43 in eczema, psoriasis, Steven‐Johnson syndrome/toxic epidermal necrolysis. Methods Archival skin biopsies from patients with eczema, psoriasis, and Steven‐Johnson syndrome/toxic epidermal necrosis were identified and examined, with sister sections stained for Cx43 and imaged by confocal microscopy. All samples were compared to age and site‐matched normal skin controls. Results Epidermal Cx43 is reduced in acute eczema, absent in regions of spongiosis, and is highly elevated in subacute and chronic eczema. In plaque psoriasis, Cx43 is overexpressed in areas with psoriasiform hyperplasia with a fish‐scale‐like appearance but is lost in regions surrounding neutrophil microabscesses. Cx43 staining is strong in the neutrophils within these microabscesses. In SJS/TEN, Cx43 expression is elevated in areas bordering normal tissue but is rapidly lost in areas of keratinocyte necrosis. Conclusions Dynamic changes in Cx43 levels are seen in inflammatory skin diseases and may represent future potential therapeutic targets.