Background Colonic pseudo‐obstruction (CPO) is characterized by colonic distention in the absence of mechanical obstruction or toxic megacolon. Concomitant secretory diarrhea (SD) with hypokalemia (SD‐CPO) due to gastrointestinal (GI) loss requires further characterization. Aim To perform a systematic review of SD‐CPO, report a case study, and compare SD‐CPO with classical CPO (C‐CPO). Methods We performed a search of MEDLINE, EMBASE, Cochrane, and Scopus for reports based on a priori criteria for CPO, SD and GI loss of potassium. An additional case at Mayo Clinic was included. Results Nine publications met inclusion criteria, with a total of 14 cases. Six studies had high, three moderate, and our case high methodological quality. Median age was 74 years (66‐97), with 2:1 male/female ratio. Kidney disease was present in 6/14 patients. Diarrhea was described as profuse, watery, or viscous in 10 patients. Median serum, stool, and urine potassium concentrations (mmol/L) were 2.4 (range: 1.9‐3.1), 137 (100‐180), and 17 (8‐40), respectively. Maximal diameter of colon and cecum (median) were 10.2 cm and 10.5 cm, respectively. Conservative therapy alone was effective in five out of 14 patients. Median potassium supplementation was 124 mEq/d (40‐300). Colonic decompression was effective in three out of six patients; one had a total colectomy; three out of 14 had died. The main differences between SD‐CPO and C‐CPO were lower responses to treatments: conservative measures (35.7% vs 73.6%, P=.01), neostigmine (17% vs 89.2%, P<.001), and colonic decompression (50% vs 82.4%, P=.02). Conclusion SD‐CPO is a rare phenotype associated with increased fecal potassium and is more difficult to treat than C‐CPO. Colonic pseudo‐obstruction is not usually associated with secretory diarrhea and severe hypokalemia (SD‐CPO). Renal disease may be a predisposing factor for the development of SD‐CPO. Patients have worse response to conservative therapy, neostigmine, colonoscopic decompression, and cecotomy. Patients may have higher mortality than observed with classical CPO. A trial of colonic decompression with concomitant use of potassium‐sparing agents is warranted, with close monitoring of potassium levels. SD‐CPO phenotype requires a distinctive clinical approach in diagnosis and management.