Patients with chronic idiopathic urticaria (CIU)/chronic spontaneous urticaria sometimes report systemic complaints (SCs). We sought to determine the frequency and characteristics of SCs among patients with CIU, as well as the association of SCs with disease measures, basophil histamine release, and serum tryptase. Adult patients with CIU were recruited from a university allergy clinic. Patients completed a disease symptom survey and underwent blood sampling for subsequent basophil histamine release and serum tryptase measurement. A total of 155 patients with CIU were surveyed, with 103 reporting SCs with concomitant hives as follows: joint pain or swelling (55.3%), headache/fatigue (47.6%), flushing (42.7%), wheezing (30.1%), gastrointestinal complaints (26.2%), and palpitations (9.7%). Patients with SCs (CIU-SC) were compared with those with no SCs (CIU-NSC). Both groups had similar demographic characteristics (average age in 40s, majority female and white) and basophil histamine release profiles. CIU-SC had significantly greater disease duration (51.5% CIU-SC vs 30.8% CIU-NSC had >4 years duration), emergency department visits (41.7% vs 23.1% had >1 visit in the last year), CIU-related work absences (65% vs 27.5% had >1 day), oral corticosteroid use (84.5% vs 59.6%), quality-of-life impairment (76.1 vs 59.2 SkinDex score), and serum tryptase levels (5.1 ng/mL vs 3.9 ng/mL). Despite similar demographic characteristics and basophil profiles as patients with CIU-NSC, patients with CIU-SC have features of greater disease burden (work absences, emergency department visits, and corticosteroid use), quality-of-life impairment, and baseline serum tryptase levels.