This perspective paper used a grounded theory method to synthesize evidence proposing that sodium toxicity from excessive dietary salt intake is a potential common pathophysiological mechanism that mediates the association of hypertension, obstructive sleep apnea, and anxiety with cardiovascular disease and COVID-19. Increased anxiety in these conditions may be linked to a high-salt diet through stimulation of the sympathetic nervous system, which increases blood pressure while releasing catecholamines, causing a “fight or flight” response. A rostral shift of fluid overload from the lower to the upper body occurs in obstructive sleep apnea associated with COVID-19 and cardiovascular disease, and may be related to sodium and fluid retention triggered by hypertonic dehydration. Chronic activation of the renin-angiotensin-aldosterone system responds to salt-induced dehydration by increasing reabsorption of sodium and fluid, potentially exacerbating fluid overload. Anxiety may also be related to angiotensin II that stimulates the sympathetic nervous system to release catecholamines. More research is needed to investigate these proposed interrelated mechanisms mediated by dietary salt. Furthermore, dietary interventions should use a whole-food plant-based diet that eliminates foods processed with salt to test the effect of very low sodium intake levels on hypertension, anxiety, and obstructive sleep apnea in cardiovascular disease and COVID-19.