1918年3月4日之後的某天,載著306名船員及乘客的獨眼巨人號在聖基茨島附近失蹤,為直至目前為止美國海軍史上非直接受戰火波及下減員最多的船隻意外。由於時值一戰期間,且其上載有10,800長噸(11,000公噸)用於生產軍火的錳礦石,美軍與史學家等人皆推測她的失蹤原因為被德意志帝國海軍俘獲或擊沉,但德軍當下和戰後都否認與事件有關[1]。美國海軍歷史與遺產司令部(英语:Naval History & Heritage Command)認為獨眼巨人號「可能被突如其來的風暴殺了個措手不及」[2],但該船失蹤的真正原因依然不明。
獨眼巨人號在1918年2月16日從巴西里約熱內盧出海,並於四天後駛達巴伊亞州首府薩爾瓦多。同月22日又載著錳礦石出發,啟程前往美國馬里蘭州巴爾的摩,期間無中轉港。在離開巴西前,船長喬治·W·沃利(George W. Worley)提交了一份稱右舷發動機氣缸破裂、無法運作的報告,但調查委員會收到報告建議返航美國後再從長計議。同時該船被認為已超出8,000長噸(8,100公噸)的最大載量,但還是獲得放行。即使如此,她隨後還是因為水位超過載重船舶吃水線(英语:Waterline)(表明已超載)[1],而被迫在巴貝多作計劃外的停泊,然而在里約熱內盧的例行檢查卻表明裝船貨物捆扎妥當[5]。獨眼巨人號在3月4日再次啟航駛向巴爾的摩,並據傳在五天後於維吉尼亞州外海碰見糖蜜液貨船「阿莫爾科號」(Amolco)[1],但阿莫爾科號的船長對此予以否認[6][7]。此外,她預定要到3月13日才抵達巴爾的摩[8],因此極不可能在9日便駛到維吉尼亞附近,畢竟當時該地距巴爾的摩的航程只需一天時間。但無論如何,獨眼巨人號最終都未能到達其目的地,也從未發現過這艘船的殘骸[9][10]。
美國海軍少將喬治·范德烏爾斯(George van Deurs)表示獨眼巨人號失事可能出於結構失效(英语:structural failure),理由為其兩艘姊妹船在運載具腐蝕性的金屬時,都遇到了沿著船殼首尾延伸的工字梁遭腐蝕的問題。此問題在傑森號煤船(英语:USS Jason (AC-12))上得到了明確的觀察,也據信是另一艘在平靜海面上斷成兩截的貨船「恰奇號」(Chuky)沉沒的原因。此外,獨眼巨人號面對的可能是風速達30—40節(56—74公里每小時;35—46英里每小時)的風暴,在這種情況下,浪距的長度足夠讓船頭和船尾同時維持在不同的浪峰之上,但由於其他部分不被海水支撐的關係,本就脆弱無比的舯部必然會承受額外的壓力[13]。
Department's 15th. Confidential. Master CYCLOPS stated that required six hundred tons coal having sufficient on board to reach Bermuda. Engines very poor condition. Not sufficient funds and therefore requested payment by me. Unusually reticent. I have ascertained he took here ton fresh meat, ton flour, thousand pounds vegetables, paying therefore 775 dollars. From different sources gather the following: he had plenty of coal, alleged inferior, took coal to mix, probably had more than fifteen hundred tons. Master alluded to by others as damned Dutchman, apparently disliked by other officers. Rumored disturbances en route hither, men confined and one executed; also had some prisoners from the fleet in Brazilian waters, one life sentence. United States Consul-General Gottschalk passenger, 231 crew exclusive of officers and passengers. Have names of crew but not of all the officers and passengers. Many Germanic names appear. Number telegraphic or wireless messages addressed to master or in care of ship were delivered at this port. All telegrams for Barbados on file head office St. Thomas. I have to suggest scrutiny there. While not having any definite grounds I fear fate worse than sinking though possibly based on instinctive dislike felt towards master.